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pmc-6501254-1 | A 56-year-old man was transported to our hospital because of massive melena and loss of consciousness. He was a current smoker with a history of hyperlipidemia. Physical examination revealed no inguinal pulse. He complained of mild chronic claudication despite having no impotence, and computed tomography revealed aortoiliac occlusive disease owing to atrophy and calcification of the terminal aorta and iliac arteries. His vital signs included a blood pressure of 135/70 mmHg and pulse of 90 beats/min. The white blood cell count was 16,300 cells/mm3, hemoglobin was 10.5 g/dL, and C-reactive protein level was 1.93 mg/L. A 35 mm thoracoabdominal aneurysm with intra-aneurysmal gas was seen on enhanced computed tomography (), consistent with an infected thoracoabdominal aneurysm accompanied by Leriche syndrome.
Emergency surgery was performed under general anesthesia with the patient in the right semilateral position. The procedure began with a left thoracoabdominal incision through the seventh intercostal space. When we reached the aorta through careful retroperitoneal approach, we could not reserve the left inferior epigastric artery, running obliquely around the incision area (). The color of aortic aneurysm wall changed from yellowish-white to black-brown. The aorta was clamped above the celiac trunk because the infection had spread around the superior mesenteric artery (SMA). Then, the infected aneurysm was opened under partial cardiopulmonary bypass (CPB) via the femoral artery and vein and thoroughly debrided. The abdominal branch vessels were perfused by CPB, and the opposite femoral artery of the sending cannulation was also perfused through a sheath connected to CPB. The celiac trunk appeared normal and was not involved by the aneurysm, and the aorta below the celiac trunk was replaced. Since the aorta had a blind end because of Leriche syndrome, we used a knitted graft with four branches (INTERGARD quarto 18-9 mm; Maquet Getting Group, Tokyo, Japan) (). The SMA and right renal artery were reconstructed using the right graft branch, and the left renal artery was reconstructed with the left graft branch (Figures and ). The second left graft branch was passed to the left common femoral artery because of the left lower limb ischemia by sacrificing the inferior epigastric artery. The omentum was filled around the graft and debridement cavity. The procedure time was 497 min and CPB time was 124 min. After the vessel reconstruction, a horizontal segment of the duodenum containing a 5 mm fistula was resected (Figures and ). The ends of the duodenum and proximal jejunum were closed by an intestinal two-stage reconstruction; the first stage includes removal of the aortoduodenal fistula and stump of the edges, and the second stage includes a duodenojejunostomy. And the intestinal fistula was made for feeding (). On postoperative day 1, the patient complained of severe pain in the right lower limb on sitting. A Doppler evaluation of the bilateral dorsalis pedis arteries revealed right lower limb ischemia. Femorofemoral bypass was performed using an ePTFE graft (Gore Propaten 8 mm; WL Gore & Associates, Co. Ltd., Tokyo, Japan) attached to the side of the leg graft branch ().
Streptococcus and Peptostreptococcus asaccharolyticus were isolated from the aneurysm. Vancomycin and meropenem were administered for 1 month, and a duodenojejunostomy, as the second stage, was performed on day 30 after the inflammation subsided (). Antibiotic was changed to oral levofloxacin on day 43, and the intestinal fistula was removed on day 44. The patient was discharged on day 48 and continued antibiotics at home for 6 months. To the best of our knowledge, there has been no evidence of any complications such as graft infection and pseudoaneurysm for 23 months postoperatively.
This study was approved by the Ethics Committee of Matsubara Tokushukai Hospital (approval number: 171202). The patient consented to the publication of this report. |
pmc-6501258-1 | A 67-year-old nonsmoker female patient in good general health was referred for implant placement and prosthetic rehabilitation in March 2012. She was completely edentulous and had worn full dentures in both arches for 17 years. The dentures at the time of presentation had been fabricated 3 months previously, and the patient was satisfied with the extraoral appearance of the lips and face and tolerated the vertical dimension (Figures and ). Her main complaint was the loss of denture retention even though she used denture adhesive daily. The patient did not grant permission for extraoral photography.
Two (2) duplicates of patient's maxillary dentures were fabricated. One (DentDu-Brm) for the implant planning using clear resin (Paladur; Heraeus Kulzer, Hanau, Germany) for the base and barium sulfate resin (Acryline DVT, Anaxdent, Stuttgart, Germany) for the teeth (). The second one was using the same clear resin for the base and the teeth in order to serve as a transfer guide during restoration (DentDu) (). Duplicates were checked for intraoral fit before use.
Clinical examination and cone beam computed tomography (CBCT) revealed an extreme atrophy of the maxilla and mandible (Figures –).
The patient's dentures were used for impressions with an alginate material (Alginat rosa; Omnident, Rodgau, Germany) and as guides for the articulation of the casts. Analysis of the articulated casts showed large vertical distances between the maxillary and mandibular alveolar crests (2.3–2.4 cm in the premolar/molar area, 1.9 cm in the anterior area) and a horizontal distance of 1.3 cm in the anterior area (). Therefore, rehabilitation with removable restorations was suggested. As the patient refused lateral and vertical augmentation, the decision was made to refabricate implant-retained removable dentures.
Both sinuses were grafted using a bovine xenograph (CompactBoneB; Dentegris, Duisburg, Germany), and the lateral windows were covered with porcine collagen membranes (BoneProtectGuide; Dentegris). In the same session, based on the CBCT, two implants were placed in positions #22 and #27 (SB line, 3.75 mm × 11 mm, Dentegris) and loaded immediately with a bar-retained overdenture using system-specific, prefabricated, angled, and tapered abutments (). A bar was milled from type 3 cobalt-chromium-molybdenum alloy (CoCrMo; ZENOTEC NP; Wieland, Pforzheim, Germany), and a metal base (housing) was cast with CoCrMo (Ankatit, Anka Guss, Waldaschaff, Germany). Elastic plastic clips (Preci Matrice; CEKA, Waregem, Belgium) were used to retain the base over the bar ().
Five months after sinus augmentation, a total of six implants (#3, 4, 6, 11, and 13; SB line; Dentegris) were placed. CBCT planning software (Sicat Implant, Sicat GmbH, Bonn, Germany) showed that the ideal tooth position was 6.8 mm in front of the alveolar ridge (). However, one implant (left sinus, #11) could not be stabilized, so treatment proceeded with the five remaining implants.
The maxillary implants were uncovered 6 months after placement, and impressions were made using an open-tray technique and a polyether impression material (Impregum Penta Soft; 3M ESPE, Neuss, Germany). System-specific ball attachments (BATTs) with their retention elements were mounted on three implants for laboratory transfer. Access windows were created on the buccal side of the DentDu in the areas of the BATTs, and the retention elements were fixed to the DentDu with self-curing modeling resin (Pattern Resin; GC, Alsip, IL, USA). Centric jaw relation was recorded using the same resin (Pattern Resin; GC America Inc., Alsip, IL, USA; ). A master cast was fabricated, and the BATTs were mounted on the implant analogs. The DentDu with retention elements was then positioned on the master cast, and casts were articulated under the guidance of the DentDu and jaw record ().
The maxillary bar was designed using a superimposed DentDu and was positioned as far labial as possible to provide support for the denture base (Figures and ). After verification of the bar's fit, an electroformed mesostructure (ELMES; Galvanogold, Wieland) with a thickness of 0.25 mm was fabricated to conform to the shape of the bar (Figures –) [, ]. Framework was cast with CoCrMo alloy (Ankatit, Anka Guss, Waldaschaff, Germany) and tried in the patient's mouth to check its passive fit ( and Figures and ). In addition, a framework for an overdenture base was fabricated by casting CoCrMo alloy (Ankatit, Anka Guss; and Figures and ). The U-shape framework covering the entire ridge including the lingual slope and partial palatal coverage provided rigidity and gains some degree of stability and support from the tissue. To provide passive retention and locking, two swivel-type lock attachments (swivel-type lock, Heraeus Kulzer, Hanau, Germany) were cast with a gold alloy (Hera; Heraeus Kulzer) ( and Figures and ) [].
The fabricated maxillary bar was mounted on the implants, the ELMES was placed on the bar (), and the jaw relationship was verified with the framework in place (). Subsequently, the ELMES was fixed to the framework using a self-cure compomer (AGC Cem, Wieland; ). Denture teeth (SR; Ivoclar Vivadent, Ellwangen, Germany) were set and tried in before the finishing process. The denture was finished with the use of an autopolymerizing acrylic resin base material (PalaXpress Ultra; Heraeus Kulzer; Germany) and delivered back to the office on the same day (Figures –) [–, , ].
The patient was then enrolled in a 6-month maintenance program. During the three years of observation period, at the follow-up visits, oral hygiene was reinforced together with debridement and prophylaxis. |
pmc-6501260-1 | A 26-year-old male was referred to the Department of Prosthodontics, Faculty of Dental Medicine, University of Monastir, Tunisia, for prosthetic rehabilitation. He was suffering from microstomia resulting of radiotherapy about 12 years ago following cavum carcinoma classified T3N0M0 (). The patient had no experience about removable complete prosthesis rehabilitation.
Oral examination revealed a limited maximal mouth opening (MMO) measuring about 21 mm, with tight and inflexible labial tissues (Figures and ).
He presented complete edentulous maxillary and mandibular resorbed ridges.
Restricted oral access made it difficult to make primary impression using classic stock impression trays. Hence, the choice was made to fabricate a mandibular sectional impression tray for each half of the arch by manually molding soft wax to the ridge, intraorally (). Then, the sectional special trays were reinforced by the autopolymerizing acrylic resin extraorally (). They were inserted into the patient's mouth in two separated pieces: left and right.
For the maxillary arch, the impression tray was made in one piece as the same manner as the mandibular one.
The preliminary impressions were made with irreversible hydrocolloid impression material (alginate).
The maxillary impression was made on one step ().
The two mandibular hemi-impressions were made separately (Figures and ). Recording the anterior ridge, in addition to the corresponding side, by each hemi-impression is an indispensable condition to validate it.
First, the right mandibular hemi-impression was poured with type II dental plaster to obtain the right sectional primary cast. After it was set, and thanks to the central common area of the two hemi-impressions, the left hemi-impression could be positioned on the right sectional cast and poured. It was held with finger pressure until plaster was set ensuring not to displace the first sectional cast seated in the impression. So, we got an entire primary cast.
For the secondary impression, single custom trays were fabricated for each arch using autopolymerizing acrylic resin. Once placed intraorally, it was carefully positioned onto denture-bearing areas and molded to appropriate contour using functional and manual manipulation. Care was taken during border molding to correctly record the peripheral extension, as the vestibular depth and width were shallow (Figures and ). Final impressions were poured to get final casts.
Mandibular movements become restricted because of facial skin fibrosis, muscular atrophy, and temporomandibular joint damage, which make recording the maxillomandibular relationship problematic. By making the mandibular record base, as possible, shorter and thinner and with patient cooperation, jaw relation record was obtained with the use of occlusion rims oriented to the established vertical dimension of occlusion, the anatomic occlusal plane, and the patient's centric relation (). The mandibular wax occlusal rim thus obtained was very short because of the reduction of the vertical prosthetic space which complicated the teeth arrangement ().
Because of a lack of teeth in appropriate sizes and shapes, conventional artificial teeth were reshaped to be managed in the available transversal and vertical space (Figures –).
During the try-in stage, the stability and occlusion were verified and the esthetic aspect was accomplished ().
After teeth arrangement, complete dentures were fabricated with the usual laboratory procedures using heat polymerized polymethyl methacrylate resin. After bench cooling, the dentures were finished and polished ().
At the insertion appointment, the balanced occlusion was adjusted (). Oral hygiene instructions and prosthesis insertion and removal were imparted. Routine follow-up appointments were scheduled after a week. The patient was satisfied with the esthetics and functional ability of the dentures. |
pmc-6501260-2 | A 47-year-old edentulous female consulted at the prosthodontic department of the Faculty of Dental Medicine of Monastir, Tunisia. She had extremely unuseful maxillary complete denture ().
Her lips were stretched, and she had a limited oral opening with a diameter and circumference of approximately 27 mm and 98 mm, respectively, resulting from cervical radiotherapy (). Her alveolar crest was sufficiently high, but her buccal and labial mucosas were thin and the saliva quantity and flowability were inadequate.
The treatment plan consisted of fabricating complete dentures with proper extension of the flanges.
With effort, preliminary impressions for both arches were obtained with flexible impression trays: a putty silicon impression material was inserted, and once placed intraorally, it was carefully molded by finger pressure covering the entire important anatomic regions using functional and manual manipulation.
Due to flexibility, the silicone tray could be easily removed ().
A light silicone material was injected on the first impression, then, the light body wash impression was made by reinserting the silicone tray in the oral cavity ().
The custom trays for the final impressions were fabricated with autopolimerized acrylic resin on each primary stone cast ().
For the mandibular impression, the oral opening was sufficient for the custom tray to be inserted on the patient's mouth.
The maxillary custom tray was cut into two unequal sections, so that the labial frenum is recorded accurately in the impression. The two segments of the tray are joined using nick and notches (). This facilitated the reassembling of the impressions outside the mouth. The insertion and movement to interlock the tray segments should be rehearsed in the mouth prior to the impression procedure.
The maxillary impression tray was inserted into the patient's mouth in two separate pieces, left and right. The fit of the borders was evaluated. Then, the peripheral borders of the trays were trimmed so that they were 2 mm shorter than the depth of the vestibule to allow space for the border-molding material. This latter was separately done for each half.
Final maxillary impressions were made by using polysulfide material alternately for the first and second halves of the sectional trays. After the impression paste set, the right and left tray segments were removed separately. The acrylic resin halves were carefully joined extraorally, and minor discrepancies at the seam were filled with soft impression wax ().
Final impressions were boxed and gently poured to get final casts (vibrator) (Figures –).
On final casts, record bases were fabricated and occlusion rims were prepared.
After making a centric relation record, transferring the record from the patient to a semiadjustable articulator was done (Figures and ).
Because of the lack of the prosthetic vertical space between the arches, the record bases were removed from the casts and replaced with thin slices of wax that supported the teeth arrangement (Figures –).
The try-in was evaluated to verify jaw relations and teeth arrangement. After patient acceptance, final festooning and flasking of the dentures were completed.
The final dentures were manufactured using similar designs to that of the record bases. The prostheses were deflasked, finished, and polished. The patient was provided with instructions for cleaning, inserting, and removing the prostheses (). She was recalled for follow-up visits to check for the maintenance and her adaptability with the new dentures. Initially, the patient felt difficulty in the insertion and removal of denture, but progressively, she became used to. |
pmc-6501261-1 | A 64-year-old male, chronic smoker, construction worker, and avid hunter presented with a one-week history of confusion and staggering gait leading to a fall. He also complained of cough productive with black sputum. Family and travel histories were unremarkable; however, social history was remarkable for a recent devastating flood in the town where he lived that sustained a large amount of water and mud damage. On presentation, his vital signs were normal. On examination, the patient was alert but not oriented. On chest auscultation, decreased breath sounds were noted in the left lower lobe. Neurological, cardiovascular, and abdominal examinations were otherwise within normal limits. His initial set of labs revealed mild leukocytosis, a negative procalcitonin, and hyponatremia. Chest X-ray (CXR) demonstrated left lower lobe pneumonia. With this information, he was therefore thought to have community-acquired pneumonia and was initiated on azithromycin 500 mg intravenous (IV) daily, ceftriaxone 1 g IV daily, and IV hydration.
Due to his initial neurologic complaints, a brain computed tomography (CT) was completed (), demonstrating a left frontal mass with surrounding cerebral edema and midline shift. Brain magnetic resonance imaging (MRI) () described the lesion as a conglomeration of multiple left frontal lobe enhancing masses causing midline shift. This prompted the differentiation of metastatic malignancy versus glioblastoma. Dexamethasone 4 mg IV every 6 hours and levetiracetam 1500 mg IV twice daily were started after neurosurgical evaluation. CT of the chest () was performed for further characterization of the lung finding on CXR with the possibility of malignancy in question. It demonstrated a multifocal mass-like area of consolidation in the left lower lobe with necrosis and cavitation interpreted as a low suspicion for malignancy with close interval follow-up recommended (). Pulmonology was consulted for evaluation with the consideration of bronchoscopy.
With the possibility of the brain lesion still being a glioblastoma, a stereotactic brain biopsy was performed first instead of a bronchoscopy. This biopsy revealed numerous light brown, long sparsely branching septated hyphae with dilated spores positive on Gomori methenamine silver (GMS) stain and periodic acid-Schiff (PAS) light green stains. Cultures were unfortunately not sent from this tissue at this time. Based on these pathology results, infectious disease consultation was sought, and empiric liposomal amphotericin 5 mg/kg IV daily with concurrent voriconazole 300 mg IV every 12 hours was initiated. At this time with a possible disseminated fungal disease on the differential, bronchoscopy was pursued. There were no endobronchial lesions present. Fungal culture of lung biopsies was completed at 35°C and revealed Nocardia. It was further speciated with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) and identified as Nocardia araoensis (). The patient was therefore treated with trimethoprim-sulfamethoxazole 1600 mg/280 mg orally every 6 hours and meropenem 2 grams IV every 8 hours. Blood cultures remained negative throughout his hospital course.
With the still unidentified fungal brain abscess and the size of the lesion portending a poor prognosis if treated only medically, neurosurgery team performed a craniotomy with the intention of complete resection. Unfortunately, only a partial resection was achievable due to the location and size of the mass. Fungal culture of the brain tissue was completed on BBL™ Sabouraud Dextrose Agar, BBL™ Inhibitory Mold Agar, and BBL™ Brain Heart Infusion Agar with 5% Sheep Blood (BD Biosciences: Becton, Dickinson and Company, Sparks, MD) with mold isolated after 6 days after inoculation at 35°C. The isolates were described as velvety green-brown in color with very long chain length, minimal branching, and oval conida. Visual identification was made as Cladophialophora bantiana (Figures and ) after 20 days, referencing Larone's “Medically Important Fungi” text []. The patient was treated with concurrent liposomal amphotericin B and IV voriconazole for the first 5 days and then voriconazole alone due to its better bioavailability and central nervous system (CNS) penetration with lesser side effects.
The presence of two rare infections in an otherwise immunocompetent individual prompted an immunological evaluation including immunological levels of Immunoglobulin (Ig) A, E, G, and M, Herpes Simplex virus PCR, CD4 counts, T4/T8 ratio, B cell count, and Natural killer cell count and however did not reveal a cause of low IgG. He was therefore treated with human IV immunoglobulin (IVIG) Octagam® 5% 500 mg/kg IV. His 6 week hospital course was complicated by cachexia, physical deconditioning, poor neurological status, and aspiration pneumonia with recurrent episodes of sepsis. Considering his poor overall state of health and grim prognosis with incomplete resection, palliative services were consulted and family decided to withdraw further medical care and transfer to hospice for comfort care. |
pmc-6501280-1 | A 21-year old male conscript presented to his unit’s medical center with headache, tiredness and fever at midnight in June, 2014. One hundred and fifty minutes later, he developed meningitis symptoms including nausea, drowsiness, confusion, stiff neck and Kernig sign. He was given 1000 mg of Amoxicillin, 1000 mg of Paracetamol and an IV dose of Ringer’s lactate solution. By 9:30 A.M., he was transferred to the emergency department of Military Hospital 108 showing symptoms of blood sepsis. He was diagnosed with meningitis and sepsis, and was treated with ceftriaxone at the dose of 1 g, four times a day. His cerebrospinal fluid was collected and a N. meningitidis culture was grown in 12 h. The obtained N. meningitidis isolate, designated DuyDNT, was typed and identified to belong to serogroup B. The patient recovered successfully after treatment.
DuyDNT isolate was revealed to be a novel sequence type and assigned an ST 13074 by PubMLST, a public database that catalogs genetic data and isolate provenance of the Neisseria genus []. By sequencing the seven housekeeping genes abcZ, adk, aroE, fumC, gdh, pdhC and pgm utilized in the MLST scheme, every N. meningitidis isolate can be assigned a sequence type (ST) and placed into groups and clonal complexes based on evolutionary relatedness []. Besides DuyDNT, only two other isolates of ST 13074 have been found, both were carrier strains identified in Vietnam in 2017 (submitted to PubMLST by our group from unpublished data). ST 13074 shared ≥ 5 identical alleles at seven typed loci with three other STs (1576, 11013 and 13455), thus making it the central ST of this group by PubMLST group’s definition (Table ). Except for isolate M3369 (ST 1576) that was identified in Italy from an invasive case, all other isolates of this group have only been detected in Vietnam, during the period from 1986 to 2017. This group do not form any clonal complex with any known isolates to date. |
pmc-6501317-1 | A 48-year-old Asian man was treated with Ozurdex™ intravitreal injection for uveitis secondary to sarcoidosis in his right eye. The diagnosis of sarcoidosis was presumptively made as he had compatible clinical evidence of hypercalcemia with raised serum angiotensin-converting enzyme (ACE) and radiological manifestations, such as bilateral hilar adenopathy, on chest X-ray after excluding other diseases that may present similarly.
He initially complained of seeing floaters over his right eye. The visual acuity of his right eye was 6/24 whereas his left eye was normally recorded as 6/6. The initial intraocular pressure (IOP) for both eyes were within the normal range (16 mmHg bilaterally). A slit lamp examination revealed right eye perivascular sheathing and Standardization of Uveitis Nomenclature (SUN) grade 2 vitritis changes. Despite intensive topical steroid treatment for 6 months, the vitritis persisted with no significant IOP increment; hence, an Ozurdex™ intravitreal injection was planned.
An ophthalmic trainee performed the procedure under aseptic conditions using the standard technique under supervision. The trainee did not notice significant recoil force generated throughout the Ozurdex™ intravitreal injection.
On day 7 post-procedure, this patient had a routine follow-up visit at the medical retina clinic and the injected Ozurdex™ implant was found to be broken into two pieces and located intralenticularly with the entry site at the inferotemporal region, breaching the posterior capsule of the lens (Figs. and ). No damage to the surrounding eye structures or cataract formation was observed. A schematic diagram showing a sagittal view of the eyeball (Fig. ) aids understanding of the entry and exit points of the broken implant into the lens. The visual acuity of our patient’s affected eye at that clinic review was 6/9 on Snellen chart.
The proposed mechanism of this intralenticular Ozurdex™ implant fracture with both entry and exit sites at different areas of the posterior capsule is the possible anterior rotation and recoil force generated as the Ozurdex™ implant was injected intravitreally with the direction of the injector pointed unintentionally toward the lens (instead of pointed toward the direction of the optic disc), thereby resulting in the above clinical findings. In order to reduce the recoil force, we suggest the Ozurdex™ implant intravitreal injection be done toward the direction of the optic disc.
The posterior capsular breach occurred in two sites of the posterior capsule (as shown in Fig. ), encroaching on the visual axis; a decision was made to proceed with the right eye cataract extraction and to reposition the fractured implant. A dispersive ophthalmic viscoelastic device (OVD) was used to help protect the corneal endothelium during phacoemulsification. The right eye natural lens was successfully removed as per usual phacoemulsification steps using divide and conquer technique. The broken Ozurdex™ implant was repositioned through the already-breached posterior capsule into the vitreous cavity (which was the initial rightful anatomical position for the Ozurdex™ implant) after the natural lens removal without vitreous loss. An intraocular lens was successfully placed in the capsular bag, after the broken Ozurdex™ implant was repositioned into the vitreous cavity. Finally, a circular posterior capsule capsulorhexis was performed prior to closing up.
At 3-month follow-up, the lens remained in place and unaided visual acuity of our patient’s right eye was 6/9 with no macular edema. No posterior capsular opacification occurred and the IOP of both eyes were not raised. No endophthalmitis or retinal detachment signs were noted. The uveitis resolved completely at 3-month follow-up with no vitritis changes on fundus examination, with right eye best corrected visual acuity of 6/6 on Snellen chart. |
pmc-6501329-1 | A 32-year-old male experienced blunt trauma due to a traffic accident riding a motorcycle stuck by a truck. Then, he was admitted to our emergency department by an ambulance. At the time of arrival at our emergency department, he was conscious without any motor deficits. Clinical examination revealed severe hypoxia with SpO2 70% at 10 L/min O2, tachypnea at 42 breaths/min, and tachycardia at 154 beats/min with severe hypotension, 54/24. Breathing sounds were decreased, and flail chest and severe subcutaneous emphysema of the entire upper body were observed at the initial evaluation, as revealed by chest computed tomography (CT), brain CT, and a focused assessment with sonography for trauma (FAST) performed as early as possible. There were no intracranial hemorrhages or definitive abdominal organ injuries. Simple chest radiography and chest CT showed large bilateral hemothorax with atelectasis and severe contusions in both lungs (Figs. a, a). His blood pH, PaO2, and PaCO2 were 7.30, 84.3 mmHg (oxygen saturation, 96%), and 47.8 mmHg on a reservoir mask at 10 L/min oxygen, respectively. We diagnosed spinous process fractures at C6 and C7 (abbreviated injury scale (AIS); 2 pts), right lateral rib fractures at 1–11, left lateral rib fractures at 1–3, 5, and 7, bilateral lung contusions, bilateral hemothorax (AIS; 5 pts), a right clavicle fracture (AIS; 2 pts), and a left scapula fracture (AIS; 2 pts). The injury severity score was 33 and the probability of survival was 0.72.
At admission, we performed intubation and thoracic drainage for hemothorax. Then, we took the patient to an operating room to achieve surgical hemostasis of the bilateral hemothorax by clamshell thoracotomy for massive bleeding from chest drainage tube. We identified pleural lacerations, so we initiated the control of active bleeding there. Severe respiratory failure due to lung contusions persisted at the time of the patient’s admission to the ICU (Figs. b, b). He gradually gained increased invasiveness by mechanical ventilation, so chest x-ray showed decreasing lung roentgen lucent; the PaO2/FiO2 ratio (PFR) was 112 mmHg with a positive end expiratory pressure (PEEP) of 20 cm H2O, and after thoracotomy, at an inspiration pressure of 33 cm H2O, arterial blood gas analysis showed that the pH, PaO2, and PaCO2 were 7.41, 73.1 mmHg (oxygen saturation, 96%), and 45.5 mmHg, respectively. Therefore, we decided to establish veno-venous (VV)-ECMO (CAPIOX SP-200 TERUMO Cardiovascular Systems, Tokyo, Japan) and performed cannulation via the right jugular vein (18-Fr cannula for inflow, Toyobo, Tokyo, Japan) and the right femoral vein (24-Fr cannula for outflow, Toyobo, Tokyo, Japan). We set the mechanical ventilation at a lower pressure. After we established VV-ECMO (1800 rpm; pump flow, 4 L/min; O2 flow, 2 L/min) with standard heparin for ECMO, the bronchial bleeding and bleeding from the bilateral lung contusions increased. Therefore, we needed to check and aspirate the bleeding by endotracheal bronchoscopy (Fig. a). However, the bleeding was very severe because full heparinization (activated coagulation time (ACT) range, 180–200 s) for ECMO was used. A chest x-ray and CT scan showed increased severity of the lung contusions and hemorrhages, indicating acute respiratory disorder syndrome (Figs. c, c). Therefore, we decided to continue ECMO without heparin due to the severe bleeding while being careful of blood coagulation without other substitute anticoagulation drugs.
After conversion, the ACT normalized (Fig. a), and the bleeding from the chest drains decreased gradually (Fig. b) instead of D-dimer increased gradually (Fig. c). Then, we could control the bleeding from the lung contusions and bronchus (Fig. b), and both the lung hematomas and oxygenation recovered (Fig. d). During this period of VV-ECMO, some treatments could be performed without any issues related circuit thrombosis and oxygenation failure. We performed tracheostomy on day 9 following ventilation with a PEEP of 20 cm H2O and an inspiratory pressure of 30 cm H2O because he needed ventilation support after removing VV-ECMO because of severe chest trauma and ARDS when we checked normalized coagulation after canceling anticoagulation before ECMO weaning. Subsequently, ECMO weaning was initiated because all of his underlying diseases were removed and improvement of lung function (FiO2 < 0.35, PEEP < 10 cmH2O, PFR ≥ 250) on his spontaneous breathing after the extracorporeal blood flow was stepwise reduced to 1.5 L/min., then Gas flow is tapered mostly in parallel to the blood flow and finally shut off for 30–60 min without dyspnea or tachypnea, and VV-ECMO was stopped on day 10 (Fig. e). There were no ECMO-related complications during the course of treatment. We removed the chest drains on day 11 (left) and day 12 (right). Mechanical ventilation weaning was initiated on day 12, and he was discharged from the ICU on day 15 (Fig. f). |
pmc-6501374-1 | A 5-year-old spayed female Maltese dog was referred for management and diagnosis of a condition involving generalized seizures, ataxia, and obtunded mentation that developed after a surgery performed by the referring veterinarian.
Four days previously, the dog had underwent acute surgery to treat severe bite wounds that penetrated its abdomen due to an attack from another dog, which had occurred 4 h earlier. The dog was alert and had a Modified Glasgow Coma Scale (MGCS) score of 18 out of 18. The dog’s rectal temperature was 38.0 °C, and it had no signs indicating that it was affected by a systemic disease. Further, the dog received a blood transfusion, and anesthesia was induced by an intravenous (IV) administration of 0.4 mg/kg butorphanol. Moreover, the dog was given 5% dextrose in 0.9% normal saline with an IV administration of tramadol and antibiotics including cefazoline and metronidazole. However, the dog developed obtunded mentation immediately after surgery while generalized seizures and ataxia developed about 12 h later. The dog was then referred to the Konkuk University Veterinary Medical Teaching Hospital.
On presentation, the dog was obtunded and hypothermic (rectal temperature: 37.8 °C) and had bradycardia (heart rate: 88 beats/min), hypertension (systolic blood pressure: 174 mmHg), and a respiratory rate of 30/min. A neurologic examination revealed anisocoria (right > left), negative responses to menace, olfaction, a cotton ball test, hearing, and an absence of physiologic bilateral nystagmus. The neurologic findings indicated the presence of lesions in the forebrain and brainstem. The dog’s MGCS score was reduced to 11. Blood analyses revealed leukocytosis, non-regenerative anemia, azotemia, and elevated hepatobiliary enzyme levels (Table ). The d-dimer levels and coagulation test results including the prothrombin time and activated partial thromboplastin time were within normal ranges. On an abdominal ultrasonography, increased echogenicity throughout the abdominal cavity with gall bladder sludge and heterogenous echotextures in the liver and pancreas were observed, which were indicative of peritonitis. Based on the dog’s history and results of its clinical examination, multifocal intracranial dysfunction with elevated intra-cranial pressure (ICP) and MODS were highly suspected.
Conservative treatment was initiated to control the ICP and seizures and to correct the MODS. Mannitol therapy (1 g/kg IV over 30 min; Daihan, Seoul, Republic of Korea) was started to decrease the ICP. Zonisamide (10 mg/kg PO q12h; Dapharm, Seoul, Republic of Korea) and potassium bromide (KBr; Samchun pure chemical co., Seoul, Republic of Korea) were prescribed in order to control the seizures. The loading dose of KBr was 100 mg/kg to be administered orally 4 times a day, following which a maintenance dose of 40 mg/kg was orally administered once a day. The dog continued to have 1–2 generalized tonic–clonic seizures daily for the next 2 days. Subsequently, antibiotic therapy was initiated that included the administrations of cefazolin (30 mg/kg IV q12h; Korus pharm, Republic of Korea), enrofloxacin (5 mg/kg SC q12h; Bayer, German), and metronidazole (15 mg/kg IV q12h; Daihan, Seoul, Republic of Korea) for the prevention of possible secondary infections. On day 2, following hospitalization, the dog’s anemia noticeably worsened, and it received a blood transfusion. Three days after hospitalization, the seizures occurred less than once every 24 h, and the heart rate and blood pressure normalized. The pupil size returned to normal bilaterally. The mental status of the dog improved, and physiologic nystagmus returned to normal. However, intermittent compulsive pacing and tight circling to the left side was detected, and the dog remained non-visual.
On the ninth day of hospitalization, the dog was still affected by blindness, impaired olfaction and hearing, and left-side circling. The dog showed a decreased ability to perform learned tasks, alterations in the sleep–wake cycles, and a decreased interest in food/treats and self-care (hygiene), all of which is consistent with a diffused forebrain disease. Magnetic resonance imaging (MRI) of the brain using a 1.5-T scanner (Magnetom essenza; Siemens, Erlangen, Germany) was performed to examine the intracranial parenchyma. There was evidence of asymmetrical diffusely increased signal intensity affecting the olfactory bulb and the frontal, temporal, and parietal grey matter bilaterally on T2-weighted and fluid attenuated inversion recovery (FLAIR) transverse images (Fig. ). The differential diagnoses for the brain lesions included edema, hemorrhagic or ischemic changes. Via hyperintense diffusion weighted imaging (DWI), an isointense apparent diffusion coefficient was observed in the same neuroanatomic areas described above, which indicated the presence of subacute cytotoxic edema that was suspected to have resulted from global ischemia (Fig. ). These findings were most consistent with GBI. In addition, severe hydrocephalus and caudal occipital malformation syndrome (COMS) were observed, which were thought to be pre-existing conditions (Fig. ). A cerebrospinal fluid sample was aseptically collected from the cerebellomedullary cistern, and the corresponding test results were unremarkable.
Following the MRI assessment, furosemide (1 mg/kg PO q12h; Handok, Seoul, Republic of Korea) and omeprazole (0.7 mg/kg PO q12h; SK Chemicals, Seoul, Republic of Korea) were added to the previous prescription to treat the hydrocephalus. Additionally, antioxidant therapy was prescribed involving the administration of vitamin E (400 IU/dog PO q24h; Yuhan, Seoul, Republic of Korea), N-acetylcysteine (20 mg/kg PO q12h; Wooridulpharm, Seoul, Republic of Korea), and pentoxifylline (10 mg/kg PO q12 h; Handok, Seoul, Republic of Korea). The general condition of the dog improved gradually over the 10-month follow-up period. The impairments in its olfaction and hearing and the blindness disappeared, but intermittent circling to the left and cognitive dysfunction related symptoms, such as an inability to recognize the owner and to recollect learned behaviors, persisted. |
pmc-6501419-1 | The 4-year-old girl described here was hospitalized in the Pediatric Ward of the General Hospital of Terni in the Umbria Region of Italy due to a productive cough over the previous 3 weeks and a fever > 38 °C associated with tachypnea over the previous 2 days. Her familial and personal medical histories were negative for relevant diseases, including respiratory infections. The child was born at term after a normal pregnancy. At admission, her physical and neurodevelopmental growth were in the normal range. However, she was febrile (axillary temperature 39.2 °C) and had dyspnea with retractions, grunting and nasal flaring. An examination revealed a respiratory rate of 40 breaths/min, heart rate of 111 beats/min, oxygen saturation in room air of 96%, and blood pressure of 104/68 mmHg. A chest examination revealed fine crackling rales in the left upper field associated with bilateral wheezing. All other systems were normal.
Chest radiography and a series of laboratory tests, including a blood culture, complete blood cell count, serum C-reactive protein (CRP) and procalcitonin levels, liver enzymes, renal function markers, and Chlamydophila pneumoniae and Mycoplasma pneumoniae antibody concentrations were performed. Moreover, a nasopharyngeal swab for the identification of respiratory bacteria and a Mantoux test were performed. A chest X-ray revealed segmental consolidation of the lingula of the left lung. Laboratory tests revealed leukocytosis (15,800 white blood cells/mm3 with 50.3% neutrophils), a slight increase in serum C-reactive protein (11.9 mg/L) and normal procalcitonin values (< 0.12 ng/mL). Blood liver enzymes and renal function markers were normal. A nasopharyngeal swab culture did not reveal viral or bacterial respiratory pathogens, including atypical bacteria. The Mantoux test was negative after 48 h, and atypical bacterial antibodies were not detected.
A blood culture revealed the presence of a Gram-negative, lactose-fermenting rod that was oxidase negative and catalase positive. The isolate was identified by means of the VITEK®2 identification system (bioMérieux, Firenze, Italy) as Ea. This identification was confirmed by sequencing the 16 s ribosomal deoxyribonucleic acid (rDNA) and comparing the result with a previously published genetic sequence. The antimicrobial susceptibility test carried out by disk diffusion method showed susceptibilities against amikacin, ampicillin, cefotaxime, cefoxitin, ceftazidime, ciprofloxacin, gentamicin, imipenem, piperacillin, piperacillin-tazobactam, and tetracycline, but was intermediate against sulfametoxazole/trimethoprim and resistant to amoxicillin-clavulanic acid, fosfomycin, and oxacillin.
Table summarizes clinical, laboratory and radiological findings at admission, during hospitalization and at the follow-up visit. The child was immediately treated orally with amoxicillin-clavulanic acid (50 mg/kg/die of the amoxicillin component in 3 doses) and erythromycin (50 mg/kg/die in 3 divided doses). Moreover, aerosolized beclometasone in saline solution was administered two times per day. The improvement in the patient’s respiratory condition was rapid. Two days after hospital admission, the resolution of her respiratory abnormalities was complete, CRP levels returned to normal values, and the aerosolized therapy was stopped. Moreover, based on the results of a blood culture and sensitivity tests, the amoxicillin-clavulanic acid medication was stopped after 3 days. Erythromycin was continued for a total of 10 days, and the child was discharged after 3 days in the hospital. Follow-up visit 1 month later did not reveal any respiratory problems.
Management of the case was approved by the Ethics Committee of General Hospital of Terni, Italy (2018-PED-02). The patients’ parents provided their written informed consent for the management of their child and the publication of the case report. |
pmc-6501452-1 | A 55-year-old, Caucasian woman was referred to our tertiary women’s heart center for persistent chest pain, palpitations, and dyspnea. Her medical history included hypertension, dyslipidemia, chronic anxiety, and bilateral non-obstructive carotid atherosclerosis. She had no prior history of diabetes mellitus, tobacco smoking, alcohol or substance abuse, or adverse pregnancy outcomes. Her family history was significant for premature coronary artery disease. Her father had a history of hypertension and had a myocardial infarction (MI) and coronary artery bypass grafting at the age of 39. Her brother had a history of coronary artery disease and also had a MI at the age of 40. Her occupational history indicated that she had been working in the field of psychology and was still an employee in the same job at the time of the hospital visit and follow-up care.
Table summarizes the general symptoms and characteristic signs of our patient for the onset of CMD and her progression to HFpEF. She had undergone an exercise treadmill test which revealed ischemic ECG changes and dyspnea. Her initial echocardiogram demonstrated a LVEF of 67%, mild diastolic dysfunction, mild left ventricular (LV) hypertrophy, no significant valvular heart disease, and no pulmonary hypertension. Subsequent invasive left heart catheterization was performed and it showed normal epicardial coronary arteries without angiographic evidence of atherosclerotic plaque. She continued to have exertional symptoms and angina-like chest pain and was subsequently referred to our center for further evaluation of suspected INOCA. During her evaluation and treatment she continued to experience stable angina and exertional dyspnea despite initial management with atorvastatin 20 mg daily, lisinopril 20 mg daily, aspirin 81 mg daily, and sublingual nitroglycerin as needed. She had a poor clinical response to sublingual nitroglycerin. Due to her persistent symptoms and abnormal stress testing, she was referred for coronary reactivity testing (CRT) to establish the diagnosis of CMD.
Our patient underwent invasive CRT, as previously published []. Testing demonstrated normal coronary flow reserve (CFR) in response to intra-coronary adenosine (CFR 3.1; normal ≥ 2.5), abnormal macrovascular endothelial function to intra-coronary acetylcholine (− 6% change in coronary diameter, constriction; normal, dilation), abnormal microvascular endothelial function (coronary blood flow change 48%; normal ≥ 50%), and abnormal non-endothelial function to intra-coronary nitroglycerin (coronary diameter change + 0%; normal dilation) (Table ). She also underwent cardiac magnetic resonance imaging (CMRI) with perfusion imaging at rest and with adenosine stress (140 μg/kg per minute) which showed circumferential subendocardial perfusion defect at stress, normal LV end-diastolic volume indexed to body surface area (EDVi) of 56.4 mL/m2, LV mass index 42.3 grams/m2, and no LV hypertrophy (septum 7.2 mm and lateral wall 6.0 mm). The myocardial perfusion reserve index (MPRI) was 1.8 which was considered borderline abnormal [] (Table ). There was no evidence of myocardial scar.
The diagnosis of CMD was established by the coronary endothelial dysfunction observed with invasive CRT, and carvedilol and eplerenone 25 mg daily were added to her regimen. She was followed regularly in clinic with good control of her blood pressure and serum lipid levels. She reported improvement of her angina and dyspnea along with reduction in the duration and frequency of these episodes.
Ten years after her initial diagnosis of CMD, our patient was hospitalized due to symptoms of dyspnea. She was found to have elevated brain natriuretic peptide (BNP) levels of 406 pg/mL and normal LVEF. She had a computed tomography (CT) angiogram of her chest to evaluate for pulmonary embolism, which was negative but revealed bilateral pulmonary edema. She was treated with intravenously administered furosemide for pulmonary edema and diagnosed as having HFpEF. Subsequently, she was discharged with instructions to increase her eplerenone.
She continued to experience worsening dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea. A repeat echocardiogram demonstrated normal LV systolic function with an LVEF of 64%, and diastolic dysfunction as evidenced by decreased lateral E′ velocity (4.2 cm/s, indicating impaired myocardial relaxation) and elevated E/E′ ratio 12.9 (suggestive of increased LV filling pressure). She underwent coronary CT angiography which showed absence of coronary atherosclerotic plaque and a coronary calcium score of 0. She was diagnosed as having HFpEF based on clinical symptoms, preserved ejection fraction of 64%, elevated BNP, and evidence of diastolic dysfunction.
As part of the WISE – Coronary Vascular Dysfunction (WISE-CVD) Continuation Study (NCT00832702), she underwent a repeat rest-stress CMRI to assess myocardial structure, function, perfusion, and scar, and 13C magnetic resonance (CMR) spectroscopy. Compared to her prior CMRI 7 years ago, she had an increase in LV wall thickness in both the septum and lateral wall (Table ). On CMR spectroscopy, the myocardial triglyceride content was elevated (0.83%) compared to normal control women (mean 0.43%), suggesting myocardial steatosis which is consistent with an ischemia-induced metabolic shift and HFpEF phenotype []. Adenosine stress first pass-perfusion CMRI again showed circumferential subendocardial hypoperfusion (Fig. ) and her MPRI worsened from 1.8 to 1.1, consistent with severe CMD []. There was no evidence of scar on late gadolinium enhancement imaging. |
pmc-6501749-1 | A 37-year-old female, indicated for IVF due to bilateral tubal factors, initiated
the ovulation induction on day 2 of her menstrual cycle. One day later, she
travelled to São Paulo on business with her mother and sister, taking the
medications. She returned and underwent an ultrasound on day 5 of the treatment,
showing a skin rash on her trunk, spreading to limbs. She reported that her
mother and sister had the same symptoms. The patient's temperature was 37ºC, and
she had mild low back pain and insignificant joint pain. A complete blood count
(CBC) did not show changes in the platelets and leukocytes. The patient and her
husband had a blood test for ZIKV using a reverse transcriptase polymerase chain
reaction (RT-PCR). The patient offered to follow the treatment until oocyte
aspiration at the clinic's expense. Oocyte aspiration was performed and seven
MII stage oocytes were retrieved. The patient's follicular fluid and cumulus
cells were donated for study in addition to her husband's semen.
This is a case report of a single-patient at our private IVF center, thus no
Institutional Review Board (IRB) approval was obtained, because our IRB
designates a single-patient case report as not subject to IRB review because it
does not meet the definition of human subjects research. Nevertheless, informed
written consent was taken from the couple. |
pmc-6501756-1 | A 47-year old woman was admitted in our emergency department after suffering from
severe abdominal pain in the hypogastric and pelvic regions for two weeks. Her
condition worsened significantly three days prior to admission. She was vomiting and
had nausea and anorexia. Her last period had occurred three weeks prior to
admission. The patient was pale and feeling ill, but did not show signs of toxicity.
Her heart rate was consistently at 110; her blood pressure was 100/70 mmHg; her oral
temperature was 38ºC; and her tilt test was negative. Her abdomen was soft,
non-distended, and she complained of mild tenderness to palpation. On auscultation,
her bowel sounds were normal. Rectal and vaginal examinations were unremarkable.
Chest X rays and ECG were both normal. Baseline workup revealed a WBC of 9700, Hb of
11, and a platelet count of 45300. Amylase, lipase, and aminotransferase readings
were normal and the patient had normal bowel movements. She reported a history of
dysmenorrhea and dyspareunia started in her teen years. The rest of her medical
history was unremarkable and she also had a normal pregnancy 14 years prior. CT
scans from 10 days prior to admission showed the large loops of her small bowel were
dilated down to the right side of the pelvic cavity. Colonoscopy, endoscopy, and
upper gastrointestinal series with Gastrografin carried out a week before
hospitalization were normal. Ultrasound examination showed an isoechoic hemorrhagic
or endometrial cyst measuring 25×15mm in diameter consistent with a ruptured
ovarian cyst, with mild to moderate amounts of fluid in the pelvis and abdomen. The
patient was in observation for six hours and her condition deteriorated. Abdominal
tenderness worsened, the patient became oliguric, and her Hb level dropped to
9.6.
The tentative diagnosis was acute abdomen due to a ruptured cyst and persistent
bleeding. She was sent to the operating room and had her abdomen opened with a
midline incision. Approximately two liters of bloody ascites were found, and a
sample was sent for cytology testing. A perforation measuring 20mm in diameter was
seen in the paramesenteric portion of the ileocecal part of the colon. The
perforation was sealed with omentum and was surrounded with pus and fecal material.
The patient underwent a right hemicolectomy and a primary end-to-end
anastomosis.
Histopathology tests revealed the ascites fluid had blood cells and reactive
mesothelial cells and no sign of malignancy. Samples of the terminal ileum, right
colon, and omentum revealed endometriosis with secondary ulceration, perforation,
and inflammatory changes of the bowel wall (). The omentum was unremarkable. |
pmc-6502262-1 | A 59-year-old female with no past medical history presented with complaints of sweats, chills, weakness, and cough for a few weeks in mid-January. She originally presented to our emergency department two weeks prior with complaints of cough, and was discharged with a suspected upper respiratory tract infection. On the day prior to this presentation, the patient noted the development of sudden onset sharp R buttock pain and redness. At presentation, patient was febrile with a rectal temperature of 102.0 F, and hypotensive to 85/55. Exam revealed bibasilar rales, a 2/6 systolic murmur best heard at heart base, and warmth and tenderness of the right hip and thigh.
Initial laboratory testing was significant for leukocytosis of 19.6/nL, 86.6% neutrophils, hemoglobin of 6.8/nL, high-sensitivity C-reactive protein of 298.69 mg/L, and erythrocyte sedimentation rate of 98 mm/h. Initial chest X-ray (CXR) was unremarkable. Blood cultures were obtained, broad-spectrum antibiotics were initiated with vancomycin and piperacillin-tazobactam (zosyn). The patient’s vital signs and hemoglobin responded to volume resuscitation and packed RBC (pRBC) transfusion. Computed tomography (CT) of the abdomen, pelvis, and right lower extremity revealed trace bilateral pleural effusions, pulmonary interstitial edema, and diffuse subcutaneous edema over the right thigh extending to the right lateral gluteal region.
Blood cultures obtained on admission grew GBS. Repeat CXR revealed new Right Middle Lobe (RML) and Left Lower Lobe (LLL) infiltrates. Antibiotics were switched from vancomycin and zosyn to ceftriaxone. Magnetic Resonance Imaging (MRI) of the spine was negative for osteomyelitis or epidural abscess, and CT chest revealed filling defects consistent with pulmonary embolism in the apical segment of Right Upper Lobe (RUL) pulmonary artery and anterior mediastinal basilar artery of LLL, and a wedge-shaped opacification of the LLL concerning for pulmonary infarction.
This array of findings led to concern for IE. The patient was switched back to vancomycin and zosyn. A Transthoracic Echocardiography (TTE) was performed and it revealed moderate Tricuspid Regurgitation (TR) but no echocardiographic evidence of vegetation on any of the valves (). Repeat CT chest was remarkable for persistent bilateral pulmonary emboli in segmental and sub segmental branches of the RUL, Left Upper Lobe (LUL), and LLL, and progressive multifocal alveolar airspace disease, concerning for multiple Septic Pulmonary Emboli (SPE).
Patient underwent Transesophageal Echocardiography (TEE), which revealed Right Atrium (RA) and Right Ventricle (RV) dilation with severe TR, TV annulus dilation, and a mobile 1.9×1.4 cm hypodensity consistent with vegetation (). Patient was transitioned back to ceftriaxone, and was evaluated by the cardiothoracic surgery team. The patient underwent repeat TTE which showed continued evidence of endocarditis. Since the patient did not have recurring fevers and did not show signs of heart failure, medical management was deemed the best management strategy. Ergo, the patient completed a 6-week course of IV antibiotics. |
pmc-6502284-1 | A 53-year-old mentally retarded male was brought to our emergency room after vomiting a plastic glove. The patient had two weeks history of intermittent nausea and vomiting. Computed tomography of the abdomen showed a non-enhancing mixed density intraluminal gastric mass (Figure ).
An endoscopy done to confirm the diagnosis and retrieve the foreign bodies was not successful. The patient was taken to the operating room and an upper midline incision was done (multiple previous abdominal surgeries). Gastrotomy and foreign body bezoars removal was performed (Figure ).
The patient did well and was discharged from the hospital. |
pmc-6502285-1 | A 24-year-old female presented non-ambulated to the emergency department of our hospital after a car accident. She was well orientated (Glasgow Coma Scale: 15/15) and was complaining of head and neck pain, dizziness, vertigo and vomiting. No other injuries except a superficial wound of the head were registered. Regarding the personal medical history, occasional headaches and vertigo treated with conservative treatment were referred from the patient. After plain radiographs and whole body computed tomography (CT) scan (our hospital's trauma protocol), no brain damage and an atlas fracture (Jefferson-type ΙΙ) with normal atlantodens interval (ADI) was identified (Figure ). As a stable fracture, the treatment was decided to be conservative and the head was immobilized into a hard cervical collar. Furthermore, the patient remained hospitalized for clinical monitoring. Forty-eight hours later, the patient continued to complain of unilateral headache and dizziness. A further evaluation with DA, CTA and brain CT scan was decided, in order the brain blood inflow and the brain parenchyma to be evaluated. No abnormal findings were detected from the brain parenchyma but the presence of unilateral VAΗ was identified (Figures , ) and further evaluation with MRA was performed for confirmation (Figure ).
After vascular surgeon’s consultation, the patient started subcutaneous low molecular weight heparin (LMWH) and remained hospitalized until the symptoms improved. She continued taking LMWH for three weeks totally.
She had a follow-up at 10 and 20 days and at two and three months post-injury. After two months, when the fracture was healed and the hard collar was removed, she started to mobilize slightly. At the two-month follow-up, no neurological symptoms were registered and after three months she had totally recovered. At three weeks post-injury, after vascular surgeon’s consultation, the patient’s treatment for the VAH changed from LMWH to antiplatelets. |
pmc-6502287-1 | A 28-year-old woman with a history of chronic neck pain in the context of myofascial pain, previously undiagnosed mild Chiari type-1 malformation, and multilevel cervical disc herniations most prominent at C4-C5, mild at C3-C4 and C5-C6 presented to the hospital with a severe postural headache for the past month. She denied significant headache history. At baseline, she had pain that radiated from the neck into both shoulders with no symptoms in her extremities. She had been treated by a pain management consultant who had performed a cervical interlaminar epidural injection which yielded no pain relief and a right-sided C4, C5, C6 medial branch block for suspected facet arthropathy six months later, again with no relief. Meanwhile, she was taking diclofenac gel, cyclobenzaprine, and tramadol as needed with limited relief from the tramadol.
She decided to seek out another pain practice and received another two rounds of cervical interlaminar epidurals nearly 11 and 12 months after the initial injections, respectively. Immediately after the 11th-month epidural, she began to develop a throbbing headache at the cervico-occipital junction that went away a few hours later with rest and acetaminophen but then returned four to five days later in an extremely intense manner. Her headache was associated with lightheadedness, nausea, and vomiting. She proceeded to have multiple visits to the emergency department (ED) over the last few days with nothing helping, including narcotics. She has tried multiple over-the-counter medications as well. On the third ED visit, three weeks after the last injection, a more detailed history revealed a clear postural component. Given the severity of her headache and associated symptoms, she was admitted for further care.
She had a repeat head CT in the ED, which was stable. The primary service had the patient sent down for a fluoroscopically guided lumbar puncture to rule out infectious and inflammatory pathology. The CSF analysis results were unremarkable, and the official reported opening pressure was within the reference range at 14 cm. The findings of the detailed neurological examination remained nonfocal and consistent throughout the hospitalization. She did have some tenderness of bilateral splenius capitis and levator scapulae muscles in her neck more so than the bilateral frontalis and temporalis muscles in her head. An MRI of her brain showed a mild Chiari I malformation with mild pachymeningeal enhancement and effacement of the prepontine cistern suggestive of intracranial hypotension (Figure ).
A cervical MRI showed no acute changes, and an MRI of the thoracic spine was initially read as normal, but a later review uncovered a thoracic epidural hematoma (Figure ).
She did not worsen, given the lumbar puncture, and there was a modest improvement in symptoms after the initiation of intravenous fluids, caffeine pills, metoclopramide, valproate, and ketorolac. However, on approximately the fourth day of hospitalization, her condition worsened, although not to the original severity on the first day when she could not sit up given the severity of the postural component. On the fifth day, she was able to walk to the bathroom and in the halls (briefly). Given her improvement, plans were made for an empiric outpatient blood patch which was performed at the L2/L3 level. She had no improvement, and the next day, she presented to the ED again where she was discharged after the headache went down to a three of 10 on the visual analog pain scale with pharmacotherapy. She developed lower back tightness and mild hip pain from the lumbar patch and continued to have headaches. Three days later, she had a CT myelogram done that showed extensive CSF leak into the epidural space in the cervical and upper thoracic spine (Figure ).
Two weeks after the myelogram, she had targeted, multi-level CT-guided interlaminar epidural blood patch injections at the C5-C6, C7-T1, and T2-T3 with subsequent complete resolution of her postural headaches. |
pmc-6502288-1 | A 65-year-old man presented with six months of progressive weakness and pain of the right shoulder, forearm, and hand. He was evaluated by his local neurologist and neurosurgeon, and an MRI was acquired and demonstrated findings consistent with a C7 nerve sheath tumor (Figure ). Electromyogram (EMG) confirmed right C7 radiculopathy, and the patient was referred to our institution for neurosurgical treatment. Although congruent findings were noted on MRI and EMG, additional history was obtained that revealed highly concerning findings inconsistent with a cervical nerve root schwannoma. The patient had several years of progressively worsening fatigue with activity, bilateral leg weakness, and shooting pain, as well as bladder urgency without incontinence. Physical examination revealed right C7 weakness, marked gait unsteadiness, and positive Babinski sign on the left.
These new findings prompted MRI of the total neuraxis, which reproduced the right C7 mass, while also identifying subtle, intrinsic T2 signal abnormalities of the thoracic spinal cord (Figure ), and multiple periventricular T2 signal abnormalities (Figure ), collectively raising significant concern for chronic demyelinating disease. Cerebrospinal fluid (CSF) analysis identified had nine oligoclonal bands with an elevated IgG index, and the diagnosis of primary progressive MS was made. Of note, the patient was assessed for benign prostatic hyperplasia, and it was thought unlikely to be responsible for his presenting urinary symptoms.
Although the diagnosis of MS provided a satisfactory explanation for the patient’s otherwise confounding symptoms, he remained with a demonstrably symptomatic cervical schwannoma, now complicated by the possible need for future immunosuppression. Correspondingly, the tumor was approached via a right posterior C6-C7 facetectomy; a gross total resection of the tumor was achieved; and a C6-T1 posterior instrumented fusion was completed, due to concern for possible destabilization in the setting of total facetectomy at a spinal level proximal to the cervicothoracic junction. Pathology confirmed a schwannoma. By post-operative day one, his right upper extremity weakness and radiculopathy were dramatically improved and had resolved by first neurosurgical follow-up at six weeks. The neurology service determined that the extent of his MS disease burden was such that initial management could be expectant; correspondingly, immunosuppression was not recommended and his other symptoms remained stable as of the last neurosurgical follow-up at one year. |
pmc-6502289-1 | We present here a case of a 46-year-old woman with a past medical history significant for a positive purified protein derivative (PPD) diagnosed in 1997 who presented to the emergency department complaining of severe low back pain. She reported that, as her pain worsened, she began to have difficulty walking, requiring a cane to ambulate. She also endorsed sensory loss below her knees, urinary incontinence, and chills without fever, however her incontinence was ostensibly related to a gynecological issue. She denied smoking, intravenous drug use, alcohol abuse, or recent travel. Her recent medical history was only significant for a mild cold several weeks ago. She presented to the emergency department for back pain two months prior and was discharged home after lumbar and sacral plain films were negative.
Physical exam on this admission was significant for diminished sensation below the knees in non-dermatomal distribution without a sensory level, full strength throughout the upper and lower extremities, and an unsteady gait, corresponding to a Frankel grade of D. Hoffman’s sign was positive bilaterally and she was diffusely hyperreflexic. Rectal tone was intact and no cranial nerve deficits were noted.
Vital signs were within normal range. Her initial labs revealed an elevated white blood cell count of 11.2 k/uL (normal 4.8-10.8 k/uL) with a left shift and erythrocyte sedimentation rate of 40 mm/h (normal 0-20 mm/h). Her C-reactive protein, basic metabolic panel, and liver function studies were within normal limits.
Full spine magnetic resonance imaging (MRI) was performed that revealed three epidural lesions distributed throughout the thoracic and lumbar spine. The largest lesion was centered at the T5 vertebral body and extended from T4-T6 causing spinal cord compression with T2 signal changes (Figure -). The lesion involved the vertebral body and was mostly T2 hypointense with contrast enhancement (Figure ). An additional T2 hypointense extradural lesion with enhancement involved the right posterior aspect of the T8 vertebral body (Figure ). The lumbar lesion was located at the L2-L3 level and extended into the right neural foramen, L2 lamina, and L2 posterior elements (Figure ). This lesion was also T2 hypointense and demonstrated contrast enhancement. At this point, the differential diagnosis was broad and included neurosarcoidosis, lymphoma, leukemia, epidural abscess, metastatic disease, and disseminated tuberculosis. She was administered a bolus of dexamethasone 10 mg due to spinal cord compression and started on dexamethasone 4 mg every six hours and broad-spectrum antibiotics. Her intact motor function in the presence of sensory disturbances (Frankel grade D), spinal stability, and disease course permitted close monitoring before her case was presented at tumor board, where the decision was made to proceed with a computed tomography (CT)-guided biopsy of the lesion at the T5 level to establish a definitive diagnosis.
CT-guided needle-core biopsy of the dominant lesion revealed noncaseating granulomatous inflammation without evidence of fungal or bacterial organisms, including acid fast bacteria, by gram, Fite, acid-fast bacilli (AFB) and Grocott-Methenamine Silver (GMS) stains, or of lymphoma or other neoplasms. Hematoxylin and eosin (H&E) stained sections show the granulomas as multiple nodules at low magnification (Figure ), composed of mononuclear histiocytes and multinucleate giant cells seen at higher magnification (Figure -). Plasma cells and lymphocytes occupy the space around and between granulomas (Figure ). These findings are all consistent with a diagnosis of sarcoidosis. Posterior-anterior and lateral chest films performed for further evaluation of sarcoid were negative: the lungs were clear and the hilar and mediastinal areas were unremarkable, showing no signs of sarcoid-related adenopathy. Also, serum angiotensin-converting-enzyme (ACE) was within normal limits at 12 U/L (normal 8-52 U/L), although this is often elevated in sarcoidosis. Cerebrospinal fluid (CSF) ACE levels were not obtained due to the strong evidence for neurosarcoidosis from the biopsy.
The patient was admitted to the intensive care unit under close neurological monitoring. A follow-up MRI was performed eight days after initial imaging and initiation of corticosteroid therapy to monitor disease response. It showed a significant reduction in the size of the posterior epidural masses centered at T5 and T8 (Figure -). Spinal cord edema was also decreased at this level. These factors, coupled with a steady increase in ambulatory stability, made the patient a candidate for discharge to acute rehab. She preferred to go home with services and was discharged on prednisone 80 mg daily on day 10 of admission.
At follow-up the week after discharge, her back pain and gait improved significantly; Karnofsky Performance Status (KPS) was reported as 90. At her latest follow-up over 18 months after initial admission, she has gainful employment, ambulates without difficulty, and is neurologically intact. |
pmc-6502773-1 | The patient was an 11-year-old female who presented to the emergency department and was admitted to the hospital in October 2016 with a 1-month history of extreme right lower extremity burning pain and seizure-like activity. MRI of back and leg were negative save for inflammation noted in the ligaments around the right knee. EEG was performed because of very frequent episodic seizure-like activity in conjunction with the pain. It was negative, so diagnosis of pseudoseizures was made. She had been treated with several drugs for the pain, including Toradol, Motrin, Tylenol, Oxycontin, and even IV morphine in the emergency department. Psychogenic causes were evaluated. Her children’s hospital records suggested reflex sympathetic dystrophy, considered because of alterations in color and temperature of her right leg, and evidence of inflammation in peri-knee ligaments.
Videos taken of the patient show her writhing in severe pain and with apparent seizure activity. After 3 months of these unrelenting symptoms (pain and pseudoseizures), she presented to the office of Dr. Robins. Informed consent was obtained. Robins provided ozone therapy by the method of direct intravenous gas (DIV). She received five treatments per week, for 26 weeks for a total of 120 treatments. She began therapy at 5 cc gas at a concentration of 55 μg/cc and was gradually increased to 30 cc at 55 μg/cc.
After 10 sessions, her pain improved and pseudoseizures diminished from 25 to 30 per day to 12–15 per day lasting ½ the previously average time of 2–3 min. After 3 months, pseudoseizures became rare and by the 4th month (120 sessions) had stopped completely, along with clearance of all pain. She returned to school symptom-free 1 year after it had begun and has stayed symptom-free since. |
pmc-6502811-1 | Within our hospital, a 59 year-old male presented with acute, severe necrotizing pancreatitis, following heavy alcohol consumption. Computed tomography scan revealed a necrotizing pancreatitis and intra-abdominal air, without a known cause. Although initially clinically stable, the patient was transferred to the Intensive Care Unit due to respiratory failure and progressive pancreatic necrosis. Over the course of four months, various isolates were cultured from aspirations and drainages (Fig. ). The isolation of Serratia marcescens and E. faecium from transgastric fluid and blood cultures prompted an antibiotic switch to meropenem and vancomycin.
Moreover, the patient was routinely screened twice-weekly for carriage of VRE, by directly inoculating the rectal swabs on VRE selection agar without PCR-based selection. During the first one and half month, thirteen swabs were taken and none yielded VRE. Yet, on day 65 of admission, a vancomycin-resistant E. faecium was isolated which had MIC values of 16 mg/L for vancomycin, 1 mg/L for teicoplanin, and 2 mg/L for linezolid (vanD-65). The isolate was analyzed by PCR and proved to be negative for vanA and vanB. Hereafter, more VRE were isolated from rectal swabs of this patient (Fig. ). The last known VRE isolate was found on day 107 of admission (vanD-107), which had MIC values of 24 mg/L for vancomycin, 1 mg/L for teicoplanin, and ≥8 mg/L for linezolid (Table ). On the 116th day of admission, antibiotic therapy was discontinued. In total, the patient had received meropenem and vancomycin for 73 days. Follow-up testing was performed at one year after discharge and the patient was asked to submit ten rectal swabs taken at least 12 h apart (i.e. spanning ≥5 days). None of the swabs yielded VRE. |
pmc-6502896-1 | A four-year-old female was referred to our hospital for the management of a partial seizure, involving the right hemisoma and associate with sialorrhea. In the post-critical time, she had difficulty with speech. An electroencephalogram (EEG), made in the emergency department, evidenced sharp peeks in the left parietal-occipital lobe. She was transferred to our department, where magnetic resonance (MR) was performed as part of diagnostic work up; the radiological investigation revealed a left parietal cortical-subcortical lesion, extending to the white matter; tumor size was 3 cm. ().
Gross total resection was performed. Histologically (), the tumor showed non-infiltrative borders and consisted of elongated tapering cells, with abundant eosinophilic cytoplasm, oval nucleus and unconspicuous nucleolus. Astroblastic pseudorosettes were observed throughout; sclerosing vessels with foamy perivascular histiocytes were present. Focally, ribbon-like or fusiform patterns were observed. Few high-cellular areas with moderate cellular pleomorphism were noticed. Immunohistochemistry revealed strong positivity for glial fibrillary acidic protein (GFAP) and OLIG2, mild dot-like and superficial positivity for epithelial membrane antigen (EMA), and negativity for synaptophysin (SYP) and cytokeratin. Proliferation index resulted about 3%; in more dense cellular areas, it reached 7–8%. According to the WHO 2016 classification, the diagnosis of low-grade AB was made. Indeed, High-grade ABs were characterized by multiple foci of high cellularity, anaplasia, increased mitotic activity (>5 mitoses per HPF), elevated proliferative index (>10%), necrosis and microvascular proliferation. |
pmc-6503032-1 | The patient is a 4-year-old boy who was the third child of apparently non consanguineous parents from Manta, Manabí, Ecuador. There was no family history of congenital ichthyosis. Gestational age was approximately 7 months. After delivery the baby was placed in an incubator, where he spent one month. His mother mentioned that at birth he had several characteristics related to a harlequin fetus: thick large fissures over the whole body, flattened nose and ears, respiratory distress and feeding difficulties that required supplemental tube feeding; although he suffered from these complications he was able to breastfeed when he left the hospital. He also had toe blisters soon after birth that converted in toes synechia, affecting his gait. During the neonatal period the patient only received topical treatments.
Physical examination revealed: ectropion, eclabium, nasal hypoplasia, rudimentary external ears, dental hypoplasia, erythema, inflammation of the gums, and almost complete alopecia (Figure a). He presented generalized scales on an erythrodermal background with abundant fissures (Figure c). Upper-extremities showed a high degree of retraction at finger joints, giving a claw hand aspect (Figure d). There were nail deformities, abundant fissures in bending sites and palmoplantar hyperkeratosis (Figure b). During the clinical examination the patient showed sensitivity and irritability, due to the pain caused by the fissures, when he moved. After obtaining informed consent, blood extraction was performed in the affected child, his parents, and his healthy sisters. Genomic DNA was isolated from peripheral blood cells using standard procedures in the Biomolecular Laboratory located in Cuenca, Ecuador and sent to the Fundación Pública Galega de Medicina Xenómica in Spain, where genetic diagnosis was carried out. Ethical approval was obtained and all research was performed in accordance with the principles of the Declaration of Helsinki. Three micrograms of patient's genomic DNA were enriched using SureSelect (Agilent Technologies) following the manufacturer's protocol. The target resequencing library was then sequenced on a SOLiD 5500xl (Life Technologies). Color space reads were mapped to the GRCh37/hg19 reference genome using LifeScope software version 2.5.1 (Life Technologies). Finally, variants were identified using GATK version 2.1 (Genome Analysis Toolkit, Broad Institute) and LifeScope version 2.5.1 and annotated with ANNOVAR version 2012Mar08. In silico prediction of potential variant effects on splicing were computed by using MaxEnt, NNSPLICE, and Splice Site Finder. Missense prediction analyses were performed by using Align GV-GD, SIFT, and Mutation Taster. All these algorithms are integrated in the Alamut® Visual 2.11 software (Interactive Biosoftware, Rouen, France). The review of the existing literature on splice-site and missense ABCA12 mutations was carried out by taking into consideration each of all carrier patients reported to date. |
pmc-6503063-1 | The proband, patient 1, was a 3-day-old female of mixed (Caucasian, African American, and Hispanic) ancestry born via Cesarean section at 35 weeks 5 days gestational age (GA) to a 26-year-old gravida 4 para 2 mother. The pregnancy was complicated by polyhydramnios starting at 21 weeks GA and continuing throughout the pregnancy. At 22 weeks 3 days GA, an intracardiac echogenic focus and nuchal thickening were noted. A subsequent ultrasound at 23 weeks 1 days GA showed the intracardiac echogenic focus and nuchal thickening had resolved but noted a left clubfoot. Another follow-up ultrasound at 28 weeks 6 days was not consistent with left clubfoot.
At birth her APGAR scores were 8 and 8 at 1 and 5 min, respectively, but around 5 min, she developed respiratory distress requiring CPAP and admission to the NICU. She was found to have multiple anomalies and dysmorphic features, including cleft palate, flat midface, hypertelorism, creases under the eyes, a small nose with anteverted nares, arachnodactyly of fingers and toes, laterally deviated great toes, and mild pectus carinatum. She was in the 99th percentile for a length of 53.3 cm at birth. She failed her newborn hearing examination in both ears. She remained in the NICU for 6 weeks due to respiratory issues and slowing feeding.
A karyotype sent at the birth hospital was normal (46, XX). During her NICU stay, a head ultrasound performed 2 days after birth showed mild prominence of the lateral ventricles and no evidence of hemorrhage. A brain MRI performed at 5 weeks of age was overall normal. At 9 weeks of age she was evaluated for bilateral wrist contractures.
Her family history is significant for a brother and father with similar physical features. Her 17-month-old brother, patient 2, previously presented at 1 day of life with a long neck, excess nuchal skin, large hands and feet with long fingers and toes, and pectus excavatum. He also had a flat midface and a saddle nose. A postnatal chromosome microarray analysis was normal. At the time, the father (patient 3) was found to have similar features including long fingers and toes, pectus excavatum, and laterally deviated great toes (Figure a,b). He also had anteverted nares and mild hypertelorism (Figure c). The father had been in generally good health his entire life. An autosomal dominant disorder was suspected due to the phenotypic similarities between the siblings and their father (Figure ). Given the family history, we decided to offer further genetic testing to determine if there was an underlying hereditary syndrome responsible for their phenotypes. |
pmc-6503126-1 | A 5-year-old girl was assessed in September 2018 for the presence of an round mass (5 cm) visible in the occipital area of the scalp, with purulent secretions, and alopecia, that persisted after a week of antibiotic treatment (oral amoxicillin and clavulanic acid 50 mg/kg per day) () (day 0). It was reported that the symptoms began following an excoriation caused by a fall. The patient also had fever and neutrophilic leucocytosis (white blood cells 13580 per μL [normal range 5200–12400], neutrophils 7850 per μL [normal range 1800–7700], lymphocytes 3900 per μL [normal range 1000–4800], monocytes 1300 per μL [normal range 120–1200], eosinophils 530 per μL [normal range 10–500]). A swab sample was taken from the scalp lesions for bacteriological and mycological examination. Hair was also collected (day +1). For the mycological examination conventional and molecular diagnostic methods by microscopic, fungal culture in Sabouraud's dextrose agar medium supplemented with 0.5% cycloheximide and 1% chloramphenicol and multiplex PCR assay was taken.
The DermaGenius® multiplex kit (PathoNostics, The Netherlands) was use for the detection the most clinical prevalent dermatophytes species. The DNA was extracted by using the PathoNostics Extraction Kit following the manufacturer's instructions. The multiplex PCR was performed according to manufacturer's instructions: 5 μl of DNA extract was added to the PCR mix and a Rotor-Gene Q (Qiagen) was used for amplification and melting curve analysis. A positive control and negative template control (NTC) were included in each PCR run.
The direct microscopic examination with 15% potassium hydroxide and glycerol showed few hyaline septate hyphae (day +1). Also the examination of lesional hair showed a positive endothrix result. The bacterial culture of the buffer was negative while Trichophyton tonsurans was detected by multiplex PCR (day +2).
After 5 day of incubation at 30 °C the colonies started to grow on Sabouraud's dextrose agar supplemented with cycloheximide and chloramphenicol, initially appearing as a grey, flat and powdery colony without red pigment (day +6). Identification of the isolate was performed by standard phenotypic methods, based on the macroscopic and microscopic morphological study. In particular, the microscopic morphological study showed that microconidia were produced in abundance, most forming loosely clustered branches, sessile, clavate, cylindrical. Few clavate macroconidia, thin-walled, was observed (day +16). The pathogen was identified as T. tonsurans. The results of mycological examinations are shown in .
Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOT MS) on a Microflex LT (Bruker Daltonics, Bremen, Germany) platform after ethanol-formic acid extraction identified the isolate as Trichophyton tonsurans (score: 2.10) (day +6). A significant clinical improvement was observed after a 8-week course of systemic griseofulvin (oral, 10 mg/die) and a 6-week course of topical econazole (1% cream, three times a day) (). |
pmc-6503133-1 | A 38-year-old woman with uncontrolled type 2 diabetes presented to the emergency room with 1 week of chills, fever, nausea, vomiting, cough and sore throat. In the emergency room, her initial exam demonstrated bilateral rales as well as mild distress. Skin, abdominal, and cardiac exams were normal. Her initial vital signs showed that she was afebrile, tachycardic to the 130s, tachypneic with a respiratory rate of 37, and O2 saturation of 98% on room air. Her initial work-up was significant for WBCs of 11,600/mm3 and glucose of 776 mg/dL with an anion gap of 20. On venous blood gas pH was 6.84 and HCO3 of 4 mmHg. Her initial chest x-ray showed a right middle and left lower lobe consolidation compatible with pneumonia ().
She developed respiratory distress and altered mental status while undergoing evaluation in the ED and required intubation and admission to the ICU for acute respiratory failure, septic shock, and diabetic ketoacidosis. She was started on broad-spectrum antibacterials as well as oseltamivir. A nasopharyngeal swab was positive for influenza B and blood cultures were positive for Streptococcus pneumoniae. A bronchoscopy performed 14 hours after admission demonstrated many Gram-positive cocci in pairs and whitish plaques in the tracheobronchial tree which were overlooked. BAL cultures confirmed Streptococcus pneumoniae infection. On hospital day 4 due to continued alteration in mental status and persistent fevers and leukocytosis she underwent Head CT and LP which were unremarkable. Due to lack of clinical improvement she underwent CT chest on hospital day 6 demonstrating multifocal nodular consolidations with early cavitation ().
On hospital day 9 Aspergillus fumigatus was finally identified on her admission BAL. She was immediately started on voriconazole. Further diagnostic evaluation included serum Fungitell ((1–3)-ß-D-Glucan) and Aspergillus antigen which were strongly positive. Repeat bronchoscopy showed a whitish collection of material in the left main bronchus () which was biopsied and revealed abundant fungal hyphae on pathology consistent with Aspergillus.
On hospital day 11 a repeat CT chest showed new large areas of cavitation bilaterally with some surrounding groundglass halos, mostly at sites of previous consolidations ().
Due to worsening cavitary disease on imaging and the burden of infection micafungin was added on hospital day 12. On hospital day 13 an MRI brain with and without contrast was ordered due to the patient's continued lack of neurological improvement which showed multifocal area of prominent T2 hyperintensity in both frontal lobes and left thalamus suggestive of CNS aspergillosis. Due to the presence of tracheobronchial aspergillosis and evidence of endobronchial spread on imaging, nebulized amphotericin B was added.
On hospital day 15, bronchoscopy showed exudate throughout the tracheobronchial tree. Cryotherapy was performed in the left upper lobe for debulking of fungal burden. For five more days she was continued on high-intensity antifungal treatment without neurological improvement. On HD 20 amphotericin B was switched from nebulized to intravenous. A repeat MRI brain on HD 20 showed unresolved lesions in the frontal lobe and some scattered 5mm foci in the left corona radiata while showing a smaller yet still present thalamic lesion (). The patient was kept on her treatment but did not have further clinical improvement. After some additional radiographic evidence of bony involvement in some of her ribs, and due to a lack of response despite antifungal treatment, she was diagnosed with overwhelming disseminated aspergillosis and her family agreed to withdraw care. On HD 25 she was extubated and expired the same day. |
pmc-6503144-1 | An 8-year-old girl suffered from intermittent abdominal pain and fever for 3 weeks. She had visited local clinics and regional hospital for several times. Oral medication was prescribed for pain and constipation, but her symptoms persisted. Then, she was brought to the Pediatrics outpatient department with nausea, vomiting and lower abdominal pain for 2 months. On physical examination, lower abdomen tenderness, and pale looking were noted. The ultrasonography (US) showed a huge pelvic tumor measuring 11.1 × 9.4 cm in size with cystic mass (3.6 × 2.8 cm) and bloody ascites over right subhepatic and lower abdominal area. There was no family history of cancer. The clinical diagnosis was pelvic mass, possibly neoplastic in nature. Computed tomography (CT) revealed a large pelvic mass, measuring 12 × 9.7 × 7.38 cm in size with internal heterogeneity and gynecological origin (ovary or urterus), enlarged paraaortic and mesenteric lymph nodes and fluid in Morrison pouch (). A three-dimensional (3D) virtual model was created from 1.25-mm thin-slice CT images and the green area illustrates the tumor (). The personal 3D model of patient's pelvic part may further improve the understanding of complex anatomy of the uterus, bladder and blood vessels. The values of tumor markers, alpha-fetoprotein (AFP), CA125 and beta human chorionic gonadotropin (hCG) were 13220.25 ng/ml, 536.7 U/ml, and <1.2 mIU/ml, respectively. The tumor was at the central pelvic cavity with direct invasion to the surrounding organs including the rectal and sigmoid colon walls, small bowel walls, the bladder wall and the cul-de-sac. In addition, it also involved the left para-adnexal tissues and the tip of appendix. Thus, the patient underwent debulking operation in which bilateral salpingo-oophorectomy, pelvic lymph node dissection, omentectomy, appendectomy, and radical excision of the implanted tumors were performed. Although the left ovary per se was grossly not involved by tumor, metastasis occurred as tumor invasion to the left periadnexal tissues and the left infundibulopelvic ligament were noted, thus left salpingo-oophorectomy was also done in order to prevent residual tumors and possible secondary surgery.
The patient was discharged 5 days after operation and recovered well. Gross examination of the specimen submitted for pathology showed a piece of necrotic tissue, measuring 3.5 × 2.0 × 0.3 cm in size. H&E stained sections of the specimen revealed tumor necrosis with small focus of atypical cells with hyperchromatic nuclei mainly in glandular or reticular pattern. Immunohistochemical staining revealed the residual cells were immunoreactive to AFP and glypican-3 (GPC-3). The findings were consistent with YST. The patient was then referred to the oncologist for further treatment and under stringent follow-up. |
pmc-6503166-1 | Patient 1 is a 5-year and 1-month-old Japanese boy. He was suffering from severe neonatal asphyxia which required mechanical ventilation since birth. Tracheostomy and gastrostomy was performed at age 7 months and 4 years, respectively. He had high-arched palate and generalized muscle weakness including facial muscles. He had acquired no head control but could sit independently at age 5 years. |
pmc-6503166-2 | Patient 2 is a 5-month-old Japanese boy. He presented with severe neonatal asphyxia. Although respiratory failure appeared soon after birth and intubation was required, he was extubated at age 7 days. He had generalized muscle weakness and did not show head control. There were no abnormalities in brain MRI, G-band karyotyping analysis, and Prader-Willi FISH test. |
pmc-6503166-3 | Patient 3 is an 18-year-old Japanese man. He was markedly hypotonic at birth and needed oxygen inhalation until 3 weeks of age. He had no difficulty in sucking and swallowing. Regardless of predominantly proximal muscle weakness, he eventually acquired head control, stood up and walked independently. At age 17 years, noninvasive positive airway pressure ventilation was started due to hypercapnia, albeit he was still ambulant. Based on Herman et al. (Herman, Finegold, Zhao, Gouyon, & Metzenberg, ), the phenotypes of Patients 1 and 2 were classified into “severe,” and those of Patient 3 were “moderate.”
None of the patients showed abnormalities in brain MRI and blood/urine biochemical examinations. Serum creatine kinase levels were within normal range in all patients. On muscle pathology in patients 1 (at age 5 years and 1 month) and 2 (at age 5 months), almost all fibers were round in shape and small in size and had peripheral halo and centrally placed nuclei (Figure a–c). In contrast, muscle pathology in patient 3 (at age 6 years) showed bimodal fiber size distribution with larger type 2 fibers and smaller clustered type 1 fibers (Figure d–f). Type 1 fiber predominance and atrophy was seen in patients 1 and 3, and type 2B fiber deficiency in patients 2 and 3 (data not shown). |
pmc-6503369-1 | Our patient is a 63-year-old Chinese male presenting with hemoptysis on a background of dysphagia and odynophagia for 1 month prior. He is a heavy smoker of 40 pack-years, has a history of hypertension and hyperlipidemia, and has not had any prior endoscopies. Physical examination was unremarkable. Given the presenting complaint of hemoptysis, a computed tomographic scan of his thorax was performed, revealing a polypoidal intraluminal soft tissue density in the upper third of the oesophagus (Fig. a, b).
An endoscopic evaluation found an exophytic oesophageal tumour with contact bleeding situated 23–30 cm from the incisors (Fig. ). Biopsy of this lesion revealed necrotic material and fragments of tumour tissue, for which the latter composed of polygonal to spindle cells associated with a fascicular arrangement in some areas. There was also significant mitotic activity and marked nuclear pleomorphism. Immunohistochemical staining for the tumour returned negative for S-100, HMB45, AE 1/3, Cam5.2, desmin, smooth muscle actin, caldesmon, CD117 and DOG-1. The pathological conclusion for the tumour biopsy was that of a malignant high-grade tumour for which the lineage could not be established given the limited tissue. Possible differential diagnoses include sarcomatoid carcinoma and malignant undifferentiated sarcoma. Further computed tomographic scans done for the staging of the malignancy did not reveal any metastasis. Preoperative lung function tests were normal, and there was no broncho-oesophageal fistula on bronchoscopy.
With the provisional diagnosis of a high-grade oesopheageal sarcoma, the patient underwent minimally invasive McKeown’s oesophagectomy. Intraoperative findings were that of an upper oesophageal tumour (Fig. ) without invasion into the airway or great vessels. The locoregional lymph nodes were not enlarged.
Examination of the specimen revealed an 11.5 × 5.3 cm polypoid mid-oesophageal tumour invading into the submucosa with clear resection margins. The tumour consisted of two histological types of malignancy within a single tumour—70% poorly differentiated spindle cell squamous carcinoma (Fig. ) and small cell carcinoma (Fig. ). On immunohistochemical staining, the nests of small cell carcinoma were positive for cytokeratin AE1/3 and cytoplasmic staining for the neuroendocrine marker synaptophysin. In contrast, the malignant spindle cells of the sarcomatoid carcinoma are negative for cytokeratin AE1/3 (Fig. ). Lymphovascular invasion was negative, and none of the three lymph nodes excised were involved by malignancy. The pathological staging of the tumour was pT1bN0.
Postoperative recovery was complicated by pneumonia with a right-sided pleural effusion. The pleural effusion was drained under radiological guidance, and mediastinal collections were conservatively managed with antibiotics. He was planned for adjuvant chemotherapy in view of the small cell carcinoma component after the resolution of the postoperative infective collections.
A repeat computed tomographic scan of the thorax 3 months postoperatively to monitor for resolution of the infective collections revealed bilateral lung subcentimetre nodules. Interval repeat scan a month later demonstrated metastasis to the lung, pleura, thoracic nodes, and liver for which a biopsy of the largest lung nodule confirmed small cell neuroendocrine carcinoma. Immunohistochemical staining was positive for synaptophysin and chromogranin, with features similar to the small cell carcinoma component of the tumour in the prior oesophagectomy specimen. There were no squamous or spindle cell components seen in the lung biopsy. He had not received the intended adjuvant chemotherapy regime, and in light of the new metastasis, he was initiated on palliative chemotherapy aimed at three weekly carboplatin and etoposide aimed at a total of 4 cycles with peglasta support. Etoposide was stopped during the first cycle due to asymptomatic bradycardia. The regime was then converted to carboplatin with irinotecan for 5 cycles. Repeat computed tomographic scan performed 3 weeks after the completion of chemotherapy showed a complete response of lung and liver metastasis and no evidence of local recurrence or distant metastasis. |
pmc-6503388-1 | A 15-year-old Chinese girl, a rural middle school student, presented with chest tightness and exercise-induced shortness of breath of 4 months’ duration. During this time, she had no obvious explanation for the gradual development of exercise-induced shortness of breath, with occasional pain in her left shoulder and back, chest tightness, limited activity, occasional cough, no fever, no hot flashes, no night sweats, and no weight loss. She was able to climb only two to three flights of stairs before resting. In the past 4 months she had not sought treatment because of her heavy learning load and insufficient attention from her parents. She was brought to our hospital by her parents for treatment because the chest tightness and the shortness of breath became more severe after activity. A physical examination on admission revealed body temperature of 36.5 °C pulse of 95 beats/minute, and blood pressure of 105/60 mmHg; there were no abnormalities in a neurological examination. A medical examination by a specialist revealed no cyanosis or dyspnea at rest. Her left thorax was full with flatness to percussion. There was breath sound asymmetry, with absence of breath sounds on the left and no dry or wet rales. The apex of her heart beat was located in the midline of her right clavicle. Blood analysis revealed white blood cells (WBC) of 5.15 × 109/L, platelets (PLT) of 118 × 109/L, red blood cells (RBC) of 5.15 × 1012/L, and hemoglobin (HB) of 144 g/L; liver and kidney function were normal. Tumor markers were as follows: alpha fetoprotein (AFP) 0.46 ng/ml, human chorionic gonadotropin (hCG) < 1 mIU/ml, ferritin 152 ng/ml, neuron-specific enolase (NSE) 12.4 ng/ml, urinary vanillylmandelic acid (VMA) 7.82 mg/24 hours. Chest color Doppler ultrasonography revealed a giant tumor with substantial echo and irregular shape. Color Doppler flow imaging (CDFI) revealed substantial visible star-like blood flow signals in the left side of her thoracic cavity (Fig. ). Enhanced computed tomography (CT) revealed a giant mixed-density mass in the left side of her thoracic cavity, part of which was fat density, measuring 323.6 mm × 193.1 mm × 175.6 mm. The enhancement of the parenchymal part of the tumor was not obvious, but it was slightly enhanced after a delay. Tumor vessels were seen in the arterial phase. Her left lung was substantially compressed into dense shadows. Her mediastinum, heart, and thoracic aorta were substantially compressed and pushed to the right. Her right lung was also compressed without hilar lymph node enlargement. The left eighth posterior intercostal artery was enlarged and the branches of the vessels entered the tumor. The branching vessels of the celiac trunk also sent enlarged and twisted branches into the tumor. Airway reconstruction revealed that her trachea and bronchus were compressed, the left part of the bronchus and the distal end were not seen, and her left diaphragm was depressed. A CT scan revealed a giant mixed-density space-occupying lesion in the left side of her thoracic cavity, originating possibly from the pleura. Radiological findings were unable to excluded malignant mesenchymal tumor (Fig. a, b).
Because of the giant tumor and the inability to exclude malignant mesenchymal tumor on radiological findings, a fine-needle aspiration biopsy was performed under ultrasound guidance to clarify the nature of the tumor. Pathological examination revealed mature fibrous adipose tissue and striated muscle tissue (Fig. a). However, the pathologists were suspicious of the result in relation to the CT scan and suggested that the tumor be re-examined; therefore, an ultrasound-guided percutaneous needle biopsy was performed again. The second time, the pathological diagnosis was possible teratoma with mature fibrous adipose tissue, striated muscle tissue, and rich mesodermal tissue (Fig. b).
After excluding malignant tumor with two needle biopsies and identifying the tumor’s feeding blood vessels by CT angiography (CTA) examination, our treatment plan was, first, embolization of the tumor’s blood vessels by digital subtraction angiography (DSA) and then, second, to remove the tumor by thoracotomy. DSA revealed that approximately 70% of the tumor was supplied by an enlarged branch of the target artery at the left eighth intercostal space, and approximately 20% of the tumor was supplied by the branch of the target artery in the celiac trunk (Fig. a, b). Using a 0.035 inch × 150 cm guidewire and a 2.7 F microcatheter, a 560 μm gelatin sponge+contrast medium 15 ml suspension was injected through the microcatheter to achieve embolization of the two target arteries. After DSA embolization, the result was satisfactory (Fig. c).
She had a mild febrile reaction after embolization. On the third day after embolization, she underwent thoracotomy through the left fifth costal oblique incision. The lesion occupied the entire left side of her thoracic cavity; the tumor had a solid intact capsule and moderate texture (Fig. a). Her left lung was severely compressed, her left hemidiaphragm was depressed, and her mediastinum, heart, and thoracic aorta were displaced to the right. After the tumor was partly removed from the center, the remaining tumor was removed from the left side of her thoracic cavity by being folded up and down. To avoid the occurrence of recurrent pulmonary edema, her left lung was suppressed by hand for approximately 15 minutes after removing the tumor and the lung was slowly re-expanded (Fig. b). The lesion size was approximately 360 mm × 200 mm × 180 mm, and the tumor weight was approximately 6.1 kg (Fig. c).
Postoperative pathological results were as follows: there was adipose tissue hyperplasia in the wide fiber interval; immunohistochemistry revealed melanA (−), desmin (−), Ki67 individual cells (+), CD34 fibers and blood vessels (+), bcl-2 (−), s100 (+), and smooth muscle actin (SMA) blood vessels (+) (Fig. a, b). The pathological diagnosis was fibrolipoma.
CT results 1 week after surgery revealed no tumor in our patient’s thoracic cavity. The upper lobe of her left lung was substantially consolidated with several cystic lesions of various sizes (Fig. ). After two fibrobronchoscopy treatments, CT results 1 month after surgery revealed improved atelectasis with several persistent cystic lesions in the left lung (Fig. ). CT results 6 months after surgery revealed that the several cystic lesions of various sizes in her left lung did not improve compared with the previous result (Fig. ). She was recommended to follow up for 1 or 2 years. If there were still cystic lesions in her left lung, her pulmonary cystic lesions would be removed.
Therefore, for giant thoracic tumors, if malignant tumor cannot be excluded before surgery and it is thought that they pose a high risk of bleeding during the operation, we recommend ultrasound-guided biopsy first, then DSA tumor vascular embolization, and finally surgical resection. The girl’s huge thoracic tumor was safely and completely removed by this method, and the prognosis is good. Otherwise, it may lead to unresectable tumors and the risk of massive hemorrhage. |
pmc-6503442-1 | A 24-year-old Caucasian descent man presented to the emergency department of our institution with an alleged history of accidental injury to the anus by compressed air jet, following which he developed diffuse abdominal pain and distention. According to the patient’s history, an air nozzle was placed at a distance of approximately 25 cm from the anus for less than 1 s. At admission, his pulse rate was 96 beats/min, blood pressure 106/70 mmHg, and respiratory rate 22 breaths/min. His abdomen was distended with diffuse tenderness and tympanic on percussion with obliteration of liver dullness. His digital rectal examination was stained with blood and fecal matter. An abdominal x-ray revealed gross pneumoperitoneum (Fig. a). He was sent for emergency laparotomy after adequate resuscitation. On exploration, a huge gush of air was noticed. The entire peritoneal cavity was soiled with fecal matter and blood. Multiple seromuscular tears (Figs. and ) were present in the sigmoid and terminal part of the descending colon with full-thickness blowout at the rectosigmoid junction. The patient underwent resection of the sigmoid colon, closure of the distal rectal stump, and end colostomy. He had an uneventful postoperative recovery and was discharged on the fifth postoperative day. Histopathological examination revealed multiple mucosal ulcerations, submucosal hemorrhages, multiple linear muscular disruptions, and perforations as mentioned. |
pmc-6503442-2 | A 30-year-old Caucasian descent man presented to our institution with compressed air insult caused by his perverted friends who put the nozzle of an air pipe (tire air pump) into his anus and inflated it. At admission, his pulse rate was 130 beats/min, blood pressure 80/50 mmHg, and respiratory rate 30 breaths/min with features of diffuse peritonitis. The patient was adequately resuscitated with crystalloids and then explored. There was a huge amount of free air in the peritoneal cavity with fecal soiling of the peritoneal cavity. There were multiple colonic perforations averaging 5 mm until the ascending colon with complete blowout of the rectum. The patient underwent total colectomy with end ileostomy and closure of the rectal stump along with copious lavage. |
pmc-6503442-3 | A 34-year-old Caucasian descent man, a petrol pump worker, presented 2 h after sustaining an alleged compressed air insult by robbers while thwarting the robbery. The robbers had thrust the compressed air nozzle into his anus. At admission, the patient was anxious with a pulse rate of 114 beats/min, blood pressure 124/76 mmHg, and respiratory rate 26 breaths/min. He had a distended abdomen with diffuse tenderness suggestive of peritonitis. An abdominal x-ray revealed massive pneumoperitoneum (Fig. b). This patient had a partial anal tear, and, on exploration, a rectal blowout at the rectosigmoid junction and multiple descending colonic perforations were noted (Fig. ). The patient underwent resection of the descending and sigmoid colon with end transverse colostomy and rectal stump closure. The anastomosis to restore bowel continuity was done 2–3 months later in these cases after radiological assessment and anal tone assessment by anal manometry. |
pmc-6504014-1 | A 66-year-old male presented to the emergency department (ED) with two episodes of coffee-ground vomiting. He denied any abdominal pain, dizziness, or syncope. He had two episodes of melena in the past with status post-argon plasma coagulation (APC) for prior gastrointestinal angioectasias. Other significant medical comorbidities were chronic alcoholism, cirrhosis, and hypertension (HTN). He had no family history to note. Other than age, he had no specific risk factors for angioectasias; most notably, there was no history of aortic stenosis, von Willebrand disease, or chronic renal failure. His blood pressure (BP) was 115/70 mmHg and heart rate (HR) was 98 beats per minute (bpm) while supine and 93/65 mmHg and 110 bpm while standing. He was afebrile, alert, and oriented to time, person, and location. A physical examination showed multiple spider nevi and a cherry angioma. Abdominal examination was significant for shifting dullness and caput medusae in the abdomen. There was no abdominal tenderness or asterixis. The neurological exam was unremarkable. The hemoglobin level at the time of admission was 6.5 g/dl as compared to the baseline 11 g/dl measured three months ago. He was appropriately resuscitated with intravenous fluid and blood transfusion. Abdominal ultrasound revealed surface nodularity and increased echogenicity with irregular appearing areas consistent with cirrhosis with model of end-stage liver disease (MELD) score 13 and Child Turcotte Pugh score (CTP) 10.
Esophagogastroduodenoscopy (EGD) was performed and revealed multiple angioectasias in the gastric body, antrum, and first part of the duodenum (Figures -). Since the patient had two earlier sessions of APC in prior admissions without improvement and a recurrence of melena, he opted for medical therapy with thalidomide, as he was not comfortable with estrogen therapy due to the possible adverse effects of estrogen.
Figure reveals an image from a prior EGD showing the application of APC for angiodysplasia.
The patient started taking thalidomide 100 mg four times a day. He was treated for a total of six months and EGD showed a marked improvement in angiodysplastic lesions (Figure ). He was followed for two years after the treatment without a recurrence of GI bleeding. |
pmc-6504015-1 | A 55-year-old female with a past medical history of hypothyroidism presented to the emergency department with complaint of chest pressure that radiated to her neck and jaw. The patient endorsed intermittent chest pressure, diaphoresis, nausea, and dizziness for the last two weeks. On examination, the patient was hemodynamically stable on room air. Initial electrocardiogram revealed normal sinus rhythm without evidence of ischemic changes, but initial troponin was elevated at 1.94 ng/mL. Chest X-ray was unremarkable. The patient was immediately given aspirin 325 mg, started on heparin infusion, and cardiology was consulted. Goal-directed medical therapy was started for acute coronary syndrome (ACS). The following day, cardiac catheterization was performed which revealed multivessel coronary artery disease with the appearance of spontaneous coronary artery dissection involving the terminal branch of OM and PDA (Figures -). Both of these vessels were of small caliber and not amendable to PCI. In addition, there was no evidence of fibromuscular dysplasia on femoral angiogram (Figure ). Left ventriculogram (LV gram) showed an ejection fraction of 55-60% with evidence of akinesis of the mid-inferior segment of the left ventricle. The patient was medically managed and troponin decreased during her hospitalization. Due to the patient’s history of miscarriages and intermittent loose stool, thorough workup was performed to evaluate for hypercoagulable disorders including, but not limited to, antiphospholipid antibody and celiac disease, which all came back negative. After conducting further investigation, it was brought to our attention that the patient had been taking an over-the-counter supplement, called Amberen, to treat her symptoms of menopause. She stated that this medication was just started recently and her chest symptoms correlated with the start of the supplement. The patient had an uneventful recovery and was discharged home with strict follow-up in the outpatient cardiology clinic. |
pmc-6504018-1 | A 67-year-old female sought medical attention for an initially suspected diagnosis of pneumonia in January 2012. A chest X-ray was performed and revealed a suspicious mass in the right upper lobe of the lung. A computed tomography (CT) scan of the abdomen and chest demonstrated a 3.1-cm lesion in the right upper lobe with no hilar or mediastinal lymphadenopathy and a suspicious left adrenal mass, measuring 5.2 cm (Figure ).
The patient underwent a biopsy for the lung lesion which confirmed a poorly differentiated adenocarcinoma which was also positive for thyroid transcription factor 1 (TTF-1). A staging whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan showed uptake in the right lung mass (SUV 29), and the left adrenal gland mass only (8.9). The patient was not considered a surgical candidate, which led to a referral for radiation therapy.
The patient presented to the clinic in May 2012 with complaints of mild shortness of breath upon exertion. No complaints of cough, hemoptysis, chest pain, anorexia or weight loss were reported. The patient had a history of high blood pressure and is a 40-pack year smoker. Pulmonary function testing demonstrated decreased vital capacity 1.6 L (62% predicted), forced expiratory volume in one second (FEV1) 1.0 L (49% predicted), and FEV1/forced vital capacity (FVC) ratio indicating obstructive disease. Diffusion lung capacity of carbon monoxide (DLCO) was within normal limits. Physical examination of the patient was unremarkable. The definitive diagnosis was primary adenocarcinoma of the right lung with an oligometastatic lesion to the left adrenal gland (stage IV).
SBRT treatment planning CT scans can be seen in Figures -. The left adrenal mass was treated first in June 2012 followed by the right lung mass one month later. 4D CT simulation with abdominal compression was performed for each site. Cone-beam CT image guidance was used prior to each fraction.
A dose of 30 Gy over six fractions was delivered via linear accelerator to the left adrenal mass utilizing a five-field intensity-modulated radiation therapy (IMRT) technique with six MV photons, to a prescribed isodose of 100%. The right lung mass was treated with a nine-field non-coplanar SBRT technique with a dose of 48 Gy in four fractions over two weeks, prescribed to the 80% isodoses. Treatment concluded in August 2012. Treatment was well tolerated, with a short bout of nausea reported.
The patient was diagnosed with a high-grade superficial bladder cancer in September 2012. This was treated with intravesical bacillus Calmette-Guérin (BCG).
Over the next few years, the patient underwent biannual follow-up CT scans. A CT scan in March 2013, at eight months post radiotherapy, indicated both the right lung mass and the left adrenal mass had decreased, measuring 1.5 cm and 5.0 cm, respectively. Follow-up PET scan at that time demonstrated a metabolic response at both sites with no significant uptake at both sites, thus no evidence of metastatic disease. She remains free of recurrent lung cancer just over five years later.
During a routine follow-up CT scan in March 2016, an asymptomatic transverse fracture of the lateral aspect of the right third rib with areas of sclerosis and lucency involving the right second and fourth ribs was diagnosed. The patient did not present any clinical symptoms of the fracture, as it was only evident on CT scan. The patient did not report any recent trauma or hospitalizations that would suggest another cause of the rib fracture. A bone scan that was performed to rule out possible metastasis was negative. This confirmed the rib fracture was a radiation-induced rib fracture, a late complication from SBRT.
Most recent chest-abdomen-pelvic CT in April 2017 and follow-up chest X-ray in October 2017 demonstrated no pleural effusion, no focal consolidation or new lung masses to indicate local failure. The patient remains clinically stable with local control of the primary tumour and continues with routine follow-ups. |
pmc-6504019-1 | A 63-year-old female non-smoker with a medical history significant for hypertension, obesity, chronic kidney disease, surgical history of three renal transplants (at age 47, 51, and 58 due to acute renal failure following abortive pregnancy at the age of 44 years), thyroidectomy, and parathyroidectomy presented to the emergency department with a persistent cough and shortness of breath for the past two months. She was without any fever, night sweats, weight loss, chills, hemoptysis, or hematemesis. The admission laboratory blood work revealed the following: estimated glomerular filtration rate (eGFR) 28.24 ml/min (normal (N):> 60 ml/min), blood urea nitrogen (BUN) level 49.2 mg/dl (N:10-26 mg/dl), creatinine 1.81 (N:0.4-1.1 mg/dl), serum calcium 12.4 (N:8.4-10.5 mg/dl), hemoglobin (Hb) 10 g/dl (N:12-15.4 g/dl), hematocrit (Hct) 30.4 (N:35-46.9%), and neutrophils 83.2% (N:42.0-76.0%). The home medication list included immunosuppressive agents tacrolimus, prednisolone, mycophenolic acid, cinacalcet, and carvedilol. The chest X-ray was non-significant; however, the admission CT scan revealed multiple focal areas of ground-glass opacities throughout both lung fields, predominantly in the upper lobes and a 3 mm sub-pleural nodule in the right middle lobe. The patient was diagnosed with pneumonia and prescribed antibiotics. Five days later the patient complained of worsening of cough and dyspnea. A repeat CT scan showed diffuse bilateral ground-glass densities in the right and left upper and lower lobes along with the presence of a newly developed 3 mm sub-pleural nodule in the right lower lobe (Figures , ).
The pulmonary function test revealed mild restrictive lung disease with reduced vital capacity (67%) and moderately reduced diffusion capacity (46%). Bronchoscopy revealed inflammatory cells in the bronchial lavage. Considering the on-going rapid progression in the patient's symptoms, two weeks later, right video-assisted thoracoscopic surgery was performed to obtain a wedge biopsy specimen from the right upper and lower lobes. The right upper lobe demonstrated extensive calcification in the interstitial compartment without significant scarring or architectural distortion, consistent with MPC (Figures , ).
The right lower lobe showed chronic interstitial inflammation with focal fibrosis and mild peri-bronchiolar metaplasia favoring the diagnosis of non-specific interstitial pneumonia (NSIP) of cellular variant type (Figures , ).
No eosinophils, pneumocystis jiroveci, or other fungal organisms were identified. The exact causative agent for NSIP was not clear in our patient but drug-induced NSIP could be considered. |
pmc-6504020-1 | A 36-year-old male intravenous drug abuser of cocaine and heroin with a history of chronic hepatitis C infection for the last 12 years presented to the emergency room (ER) with complaints of nausea, abdominal pain, decreased urine output, and dark discoloration of his urine for three days. He had reduced peroral intake due to nausea, and he otherwise denied having a recent trauma, excessive exercise, medications intake, fevers, chills, shortness of breath, dark discoloration or pale stools. He denied any current recreational drug use, but the family feared that his recent behavior over a week ago suggested recent substance abuse. His vitals upon presentation were as follows: he was afebrile and he had a blood pressure of 120/80 mmHG and a heart rate of 70 beats per minute (bpm).
Investigation
His blood work done in the ER showed elevated creatinine (Cr) of 8.26 milligrams per deciliter (mg/dl) and a blood urea nitrogen (BUN) level of 55 mg/dL. His serum sodium was 130 milliequivalents per litre (mEq/L), potassium was 5.2 mEq/L, calcium was 4.7 mEq/L, and serum CK without reflexive MB were 152 units per liter (U/L). His serum lactate dehydrogenase (LDH) was 210 U/L, serum ALT 114 U/L, and AST 54 U/L. His hemoglobin (Hb) level was 14.7 gram per deciliter (g/dL) with a normal reticulocyte count, peripheral blood smear (PBS), clotting profile and negative Coombs testing. His urine dipstick showed gross hematuria, specific gravity of 1.03 and 3+ proteinuria. A urine microscopy test showed normal 1-3 red blood cells (RBC) per high power field (HPF). A urine toxicology screen was negative. Computed tomography of the abdomen and pelvis revealed no evidence of a stone. A serum assay for complement was within standard limits. A serum panel for antinuclear antibodies (ANA), antinuclear cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane antibodies (anti-GBM) levels came back negative. Arterial blood gas (ABG) showed pH of 7.34, pCO2 of 43, HCO3 of 24. After an extensive workup, our suspicion was cryoglobulinemia-induced rapidly progressive glomerulonephritis (RPGN) secondary to the long-standing history of hepatitis C virus (HCV) infection. A left-sided kidney biopsy was consistent with normal glomerular histology on gross and electron microscopy, and pigmented tubular casts (Figure ). The immunoperoxidase staining was positive for myoglobin pigmented cast in distal renal tubules. The biopsy findings were consistent with HP-induced ATN or RM-induced ATN secondary to substance-induced RM.
Differential diagnosis
On presentation, we suspected cryoglobulinemia-induced RPGN secondary to the long-standing history of HCV infection. We were also suspicious that it could be hemoglobinuria-associated AKI due to the findings of heme positivity on urine dipstick with negative urine microscopy for RBC, but a normal PBS, reticulocyte, and bilirubin were not consistent with this etiology.
Treatment
He did not have any indication for urgent dialysis. Due to persistently abnormal kidney function with oliguria and kidney biopsy pointing towards RM-induced ATN, the patient was placed on hemofiltration (continuous veno-venous hemofiltration/CVVH) after placing a temporary catheter. The abnormal liver function test was suggested to be due to RM according to hepatology consult. So no specific action was advised regarding it.
Outcome and follow-up
His urine output started improving on Day 5 with supportive therapy. His Cr dropped significantly after undergoing temporary hemofiltration. On the 10th day of admission, his serum Cr was 1.3 and BUN was 25. He was discharged home with a close follow-up with nephrology. On follow-up at the one-month interval, his renal function was within standard limits with a Cr of 0.9 and BUN of 15. His liver enzymes had also returned to normal values at the one-month follow-up visit. |
pmc-6504022-1 | A 28-year-old male patient presented in casualty with complaints of fever with chills and rigors with pain in the abdomen for a period of 20 days. The patient had initially taken antipyretics and antibiotics but found no effect. On clinical examination, the patient was febrile, and his abdomen was soft without any guarding or rigidity. Routine investigation showed that the patient had diabetes, which was uncontrolled. The test results indicated that the patient also had a high erythrocyte sedimentation rate along with a high total leukocyte count and a high level of positive C-reactive protein. Therefore, insulin and empirical antibiotics were started immediately. An ultrasonographic examination of the abdomen revealed hepatomegaly, chronic pancreatitis, and splenomegaly with multiple splenic abscesses. An endoscopic examination of the upper gastrointestinal tract showed the presence of esophageal candidiasis with a dilated vein at the fundus. Contrast-enhanced computed tomography (CECT) of the abdomen indicated chronic calcific pancreatitis with splenic vein thrombosis, multiple splenic abscesses with evidence of rupture and ascites, and bilateral pleural effusion with basal lung collapse. Blood culture report showed the presence of B. pseudomallei, which was sensitive to imipenem and aminoglycosides, and so the patient was put on antibiotics. A few days through the course of treatment, the patient complained of low back pain. Clinical examination revealed tenderness at the bilateral sacroiliac joints with no neurological deficit. Plain radiographic examination confirmed the diagnosis of bilateral sacroiliitis and, therefore, twice-daily sulfasalazine 500 mg was added to the treatment regimen. One week later, the patient presented again with unimproved back pain and paraesthesia and weakness in both the lower limbs. On musculoskeletal examination, the power of both the lower limbs was found to be 4/5, with decreased sensation in the bilateral L4, L5, and S1 dermatomes. An examination of the upper limb showed no neurological deficit. Magnetic resonance imaging (MRI) of the spine showed abnormal hyper-intensity of C5, D1, D8, and D12 vertebra body with post-contrast non-enhancement of the portion of D12 vertebra along with anterior epidural, left paraspinal, left iliac, and sacroiliac abscesses (Figures - and Figures -).
Bilateral sacroiliitis was also confirmed by MRI examination, so emergency decompression was planned for the patient. Accordingly, a laminectomy was performed, extending from D12 to L4 vertebra without affecting facet joints and the intraoperative abscess was found to be loculated (Figures -).
Proper decompression with an evacuation of pus was done, and the obtained pus was sent to the laboratory for culture and sensitivity analysis. The culture and sensitivity report was suggestive of the growth of B. pseudomallei, which was sensitive to imipenem and aminoglycosides. Postoperatively, the neurological status of the patient improved, and he was shifted to the general surgery unit where he was operated for a splenic abscess. Intravenous antibiotics were continued for six weeks, and the patient was discharged. At the three-month follow-up, the patient had recovered completely. |
pmc-6504023-1 | A 31 weeks preterm male was born by cesarian section to a 30-year-old mother. His birth weight was 1080 gm and the circumference of his head was 27 cm. Apgar scores were 6 (1 min), 5 (5 min), and 5 (10 min). His left hand was swollen due to a constriction band and, therefore, put in an elevated position. Due to respiratory distress syndrome (RDS), non-invasive positive pressure ventilation (NIPPV) was applied for two days. Also renal failure with anuria and ischemic encephalopathy were diagnosed during the next few days. The neonate's general clinical condition was critical.
Prenatal history included twin-to-twin transfusion syndrome. At the 17th week of gestation, there was an attempt to separate the fetuses, but two days later, one of them was diagnosed dead. Three days before the delivery, the fetus was diagnosed with a constriction band around its left forearm.
The neonate was transferred to our institution’s neonatal intensive care unit on the second day after birth. A constriction band around the distal third of the forearm was noticed. Severe swelling and vascular compromise of the hand were evident (Figure ). Capillary refill time at the fingers was delayed and radial pulse was barely palpable. The hand and fingers were tense and not easily compressible. The fingers did not show any signs of spontaneous movement. Radiographs of the left forearm revealed a displaced fracture of the radius and ulna at the level of the band on the distal third of the forearm (Figure ). Abnormal motion was detected at the site of the forearm defect.
We decided to perform a reduction of the fracture and release the band. Under anesthesia and sterile preparation, a 5 mm longitudinal incision with an 11 blade scalpel over the dorsal part of the band was performed. Due to the swelling of the hand, a second 5 mm longitudinal incision was made dorsally in order to decompress it. Wounds were left open. Finally, the fracture was reduced and immobilized with a palmar cast in order to decompress the compartment syndrome (Figure ). The hand was kept elevated. Daily wound changes with loose non-circumferential gauze and monitoring of the hand revealed salvation of the limb. The edema gradually decreased and the hand became soft and compressible. Capillary refill at the fingertips and nail beds became evident and radial pulse was palpable (Figure ). Unfortunately, the patient deceased on the 16th day of his life. |
pmc-6504026-1 | A 68-year-old male presented to our hospital with complaints of weight loss, fatigue and a progressively increasing mass over the left mandibular area for the past three months. On examination, the mandibular mass was firm, with no overlying skin changes or discharge. His past medical history included type two diabetes mellitus and chronic pancreatitis diagnosed eight months ago on computed tomography (CT) of the abdomen and pelvis from an outside institution. The CT also reported a 1.4 cm mass in the left kidney. Since his renal function tests were normal and there were no systemic complaints, no further investigations were ordered. Three months later the patient noticed bilateral swelling in armpits which were identified as bilateral axillary lymphadenopathy. Fine needle aspiration cytology of the left axillary lymph node revealed chronic lymphadenitis. Consequently, the patient was prescribed antibiotics. As the axillary lymphadenopathy persisted and the patient noticed new onset cervical lymphadenopathy, an otorhinolaryngology consultation was sought and CT of the neck was performed. The CT revealed bilateral cervical lymphadenopathy and small lytic lesions in the scapula, humerus, upper ribs and cervical vertebrae. This raised the suspicion of bone marrow involvement with a differential diagnosis of a lymphoma, multiple myeloma or metastatic disease. The patient's laboratory investigations on presentation are shown in Table .
A serum immunofixation electrophoresis was ordered which revealed normal levels of serum immunoglobulins G, A, and M, decreasing the likelihood of multiple myeloma. Tissue biopsy of the mandibular lesion exhibited a tumor comprised of nests of polygonal cells with abundant and clear cytoplasm. The nuclei were round to oval and hyperchromatic. A tissue biopsy from a lesion in the left rib revealed predominantly necrotic tissue with one fragment showing a tumor. The tumor comprised of atypical, ovoid cells with hyperchromatic nuclei and eosinophilic to clear cytoplasm. An admixed lymphocytic infiltrate was also seen. Figure shows the tissue biopsy of the mandibular lesion.
A bone marrow biopsy was performed to rule out bone marrow involvement. Bone marrow trephine revealed a hypercellular marrow showing infiltration by non-hematopoietic tissue, composed of tubular structures lined by large cells with abundant and clear cytoplasm. Figure shows the bone marrow trephine biopsy.
The infiltrate was positive for cytokeratin AE1/AE3 and CD10 immunostains. CD10 is an immunostain that is found positive in proximal convoluted tubules. Figure shows a section of the bone marrow showing positivity for CD10.
This confirmed the presence of metastatic renal carcinoma, likely clear cell RCC in the bone marrow. The patient was referred to the oncology clinic for further workup to identify the primary neoplasm. |
pmc-6504027-1 | A 28-year-old male, deaf and dumb since birth, presented to the medical department (MD) of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) in November 2018 for the evaluation of generalized upper and lower limb weakness along with progressive facial puffiness (Figure ) for the past nine years. There was also a history of lower limb swelling for the past seven years.
On examination (O/E), his pulse was 82 beats/min, blood pressure (BP) was 110/70, respiratory rate (RR) was 16 breaths/min, and he was afebrile. There was no thyroid enlargement. Lower limbs showed nonpitting edema up to the ankles. Upon neurological examination, bulk showed diffuse bilateral pseudohypertrophy of the calf muscles (Figure ) and the deltoids, tone was normal, power was 4/5, reflexes were 2+, and Gowers’ sign (GS) was positive. The skin was coarse and dry with dermopathy. Systemic examination was normal.
Laboratory investigations revealed hemoglobin (Hb) of 11.7 gm/dl, raised serum cholesterol of 310 mg/dl, raised TSH of 35.2 μIU/ml [Normal (N) = 0.4-4.0], decreased levels of thyroxine (T4) of 0.14 μg/dl (N = 4.5-12.5), low plasma triido thyronine (T3) of 26.2 ng/dl (N = 84-172), anti-thyroid peroxidase antibody (anti-TPO Ab) <10 (N = <35), elevated creatine phosphokinase (CPK) of 1108 U/L (N= 85-170), creatine kinase-muscle and brain (CK-MB) of 126 U/L, elevated lactate dehydrogenase (LDH) of 930 U/L (N = 225-450), and raised serum aldolase of 9.3 U/L (N = 0-7). Blood glucose, liver function tests, blood urea, and serum creatinine were not remarkable. Abdominal X-ray revealed bilateral renal cortical cysts; however, no calculus or hydronephrosis was seen in both kidneys. Evaluation of cardiovascular and respiratory systems did not show any significant abnormality. Electromyography (EMG) and nerve conduction study (NCS) were normal. A biopsy was taken from his right deltoid muscle which showed mild changes in fiber size and local fibrosis. The findings were suggestive of myopathy. Immunohistochemistry was not done due to financial constraints.
A diagnosis of HS was made based on clinical manifestations, laboratory investigations, and confirmatory muscle biopsy report. We further suspected PS as the cause of hypothyroidism in this patient based on his symptoms of congenital deafness and thyroid dysfunction. A tone audiometry was carried out which showed bilateral sensorineural hearing loss. A diagnosis of PS was finally established by performing a perchlorate discharge test which showed an abnormally rapid loss of radioactive iodine from the thyroid gland after the administration of perchlorate.
The patient was initially treated with 100 μg levothyroxine daily which was gradually increased to 150 μg after two weeks. The patient was assessed after four weeks. His swelling resolved and TSH levels went down to 13 μIU/ml . The patient is under regular follow up with improvements in his symptoms. |
pmc-6504030-1 | A 56-year-old woman with a history of cholelithiasis and irritable bowel syndrome presented to the office for postprandial, colicky left upper quadrant pain radiating to the right shoulder lasting approximately 45 minutes. The pain was associated with three to four episodes of diarrhea and dyspepsia. Lab studies showed gastrin level off PPI of 2100 pg/mL. Ultrasound of abdomen showed diffusely increased hepatic echogenicity suggesting fatty change and cholelithiasis. The patient was sent for a hepatobiliary iminodiacetic acid (HIDA) scan that was performed, showing an ejection fraction of 90%. Elective cholecystectomy was scheduled and performed without resolution of the symptoms. The patient was sent for colonoscopy that was negative. Esophagogastroduodenoscopy (EGD) with biopsy and snare polypectomy showed erythematous “carpet-like” atrophic mucosa in the antrum, five to six sessile polyps (the largest being 10mm) with nodular mucosa in the body of stomach and fundus (Figures -).
Endoscopic ultrasound demonstrated a 2.5 x 1.5-mm isoechoic mass in the body of the stomach with invasion into the submucosa. Octreotide scan was negative for other organ involvement. Histology from gastric polyps revealed grade 2 well-differentiated GNET involving the mucosa and submucosa (Figures -).
Pathology also showed +Ki-67 in 3.8% of tumor cells with mitotic activity 0.4/10 high-power fields. Immunohistochemistry of the sample showed +chromogranin, + synaptophysin, +CD56, pankeratin, and focal CDX2+ (Figures -).
The patient was treated with endoscopic resection, pantoprazole 40 mg daily, vitamin B12, iron supplementation, and follow-up EGD in six months.
Follow-up endoscopy at six months with ultrasound has shown multiple mucosal polyps up to 10 mm in the body and fundus. Biopsies of these lesions show well-differentiated carcinoid tumors and chronic gastritis with intestinal metaplasia. |
pmc-6504031-1 | A 64-year-old female patient reported with pain and swelling in her right submandibular region, noting the pain had persisted for 10 days. She reported concerns of intermittent swelling and pain during meals, which resolved after the meal, and she reported unpleasant sensations while eating sour or acidic food. On clinical examination, we noted swelling on her right submandibular region, extraorally. There was no discharge associated with the swelling. Bimanual palpation revealed a firm swelling in the posterior floor of the mouth. We clinically diagnosed the patient as having right submandibular salivary gland sialolithiasis. The diagnosis was confirmed by computed tomography (CT) (Figure ). The process of surgically removing the gland began with a Risdon incision placed 3 cm to 4 cm below the mandible. We identified and protected the marginal mandibular nerve and then removed the submandibular gland from the mylohyoid muscle. We then divided and ligated the submandibular duct to remove the gland along with the calculi, which was an approximately 7 mm spherical formation (Figure ). We placed a suction drain and closed the wound in layers. The patient experienced no postoperative complications on follow-up evaluations. |
pmc-6504031-2 | A 36-year-old male patient reported with swelling below the tongue and pain during meals. On examination, we palpated a hard swelling on the left submandibular gland duct. The swelling was confirmed by occlusal radiograph showing radio-opacity medial to 46,47 (Figure ). We diagnosed the swelling as left submandibular salivary gland duct sialolithiasis. While the patient was under local anesthesia, we placed a stay suture to prevent the stone from gliding posteriorly. We then placed an incision over the stone to expose the calculi and facilitate its removal (Figure ). We sutured the duct at the level of the mucosa on the floor of the mouth. The calculus was roughly oval and measured 10.4 mm (Figure ). The patient experienced no postoperative complications on follow-up evaluations. |
pmc-6504033-1 | A 57-year-old nonsmoking Caucasian female was brought to the hospital by her husband due to sudden shortness of breath. Upon admission, the patient received nebulizer treatment and intravenous steroids, but her condition continued to deteriorate and required an urgent transfer to the ICU, in which she was placed on mechanical ventilation. The patient presented a few times similarly in the past couple of months, requiring mechanical ventilation every visit. According to the patient's husband, the patient had no sick contact, recent travel, or a productive cough before admission. He also stated that she did not complain of chest pain or shortness of breath upon exertion.
Upon physical exam, she was on a ventilator, resting comfortably. Her vitals were as follows: a blood pressure of 113/60 mmHg, a pulse of 108 beats per minute (bpm), a temperature of 98.0°F, a respiratory rate of 20 breaths per minute (bpm), and a pulse oximeter of 99% on 60% Fi02. The patient had expiratory wheezes heard bilaterally. The patient’s heart had regular rate and rhythm, with no murmurs, gallops, or rubs heard on auscultation. There was no jugular venous distension or peripheral edema noted in all extremities.
After admission, a computed tomography angiography (CTA) was done to rule out a possible pulmonary embolism. Results were negative, along with cardiac workup. The immunoglobulin epsilon (IgE) levels were within reasonable limits. The hematology results showed a significantly high white blood cell (WBC) count with neutrophil predominance, as shown in Table .
The patient was sent to the university hospital and seen by an immunologist and allergist. She was given Daliresp (roflumilast) along with azithromycin. Upon medication, symptoms significantly improved with no further acute asthma episodes requiring outpatient and hospitalized visits. |
pmc-6504034-1 | A 69-year-old male of Europid origin with risk factors including high blood pressure, dyslipidemia, and diabetes presented to the Clinic of Cardiology at University Hospital St. Ekaterina with symptoms of chest oppression and palpitations. Holter electrocardiography monitoring registered paroxysmal atrial fibrillation with ischemic ST changes. An echocardiography scan showed preserved left ventricular ejection fraction (62%), low-grade mitral regurgitation, moderate aortic regurgitation and initial dilatation of the ascending aorta.
The patient was planned for invasive diagnostic procedure. The coronary angiogram revealed an aneurysmal dilatation of the trunk of the LMCA with a transverse diameter of 11 mm (Figures -).
We did not observe stenosis of the coronary arteries due to atherosclerosis. The conducted aortography revealed second-grade aortic regurgitation. The ascending aorta was dilated, with a transverse diameter of 43 mm. The patient was managed non-operatively with medication therapy including a vitamin K antagonist (acenocoumarol), antiarrhythmic (amiodarone), angiotensin II receptor blocker, β-blocker and lipid-lowering medication (statin). |
pmc-6504259-1 | A 64-year-old man with no significant past medical history was diagnosed with a pulmonary nodule (diameter: approximately 0.7 cm) in the right lower lobe 2 years ago, the patient did not follow the doctor's advice to perform chest CT scan after 6 to 8 months. In a recent health check-up, chest CT showed increase in size of the nodule to 1 cm (Fig. A). VATS wedge resection of right lower lobe was planned. CT-guided hook-wire localization of the lung lesion under local anesthesia was planned before surgery using a breast localization needle (21 gauge; AccuraBLN2110, Angiotech Biomaterials, Palo Alto, CA) owing to the small size of the nodule.
The patient was placed in the left lateral decubitus position. After a positioning scale was attached to the chest wall surface, thin-section CT scan was performed to determine the puncture point and direction. The skin around the puncture point was disinfected and draped followed by injection of 2% lidocaine (5 mL) for local infiltration anesthesia. Percutaneous lung puncture was performed according to the predetermined puncture point and direction, and a 10-cm needle was quickly inserted into the lung tissue while the patient held his breath at the end of inspiration. The proper location of the needle was confirmed by a thin-section CT scan. The positioning guide wire was then deployed, the puncture needle was removed, and the guide wire was gently pulled outwards to fix the barb at its front end to the lung tissue (Fig. B). Unexpectedly, the patient suddenly lost consciousness and suffered convulsions during the pulling process. Physical examination showed: light coma, GCS score of 13 points; the pupils were symmetrical (diameter 3 mm) and reactive to light; there was no neck rigidity; limb twitching was present; and positive Babinski sign was observed on both sides. Emergency cranial CT revealed arborizing/linearly distributed gas in the territory of the right middle cerebral artery (MCA), which was suggestive of air within the cortical branches of the right MCA (Fig. A). Chest CT showed no signs of pneumothorax or any obvious abnormality of large cardiac vessels. Therefore, the patient was diagnosed with cerebral arterial air embolism. Medical treatment was administered, including hyperbaric oxygen and antiplatelet aggregation therapy. However, there was no improvement in the patient's condition. Brain CT reexamination performed 24 hours after air embolism showed disappearance of gas densities and a large infarct in the territory of right MCA with diffuse brain edema in the right hemisphere. Dehydration treatment was administered to reduce intracranial pressure; however, no improvement in the patient's condition was observed. Forty-eight hours after air embolism, cranial CT revealed aggravated cerebral edema, a marked shift of the midline structures, and subfalcine herniation (Fig. B). The patient's consciousness disturbance aggravated and the patient slipped into deep coma. The pupils were bilaterally asymmetrical and did not react to light. The patient exhibited increased difficulty in breathing. His legal guardian refused decompressive craniectomy or ventilatory support. Clinical death occurred 55 hours after air embolism. |
pmc-6504261-1 | The healthy 34-year-old woman had experienced arthralgia at the shoulders, wrists, and ankles for a period of 2 months. Subsequently, she presented with a high fever and swelling of fingers and visited a local orthopedic clinic. Thereafter, she was admitted to our hospital for further evaluation of fever of unknown origin with polyarthritis in May 2018.
On admission, her body temperature was 37.5°C, blood pressure 86/54 mm Hg, and heart rate 80 bpm. A physical examination showed swollen lymph nodes in the left neck and both axillae. Laboratory investigations (Table ) showed reduced hemoglobin (Hb) (8.7 g/dL) and albumin levels (2.9 g/dL), with elevated serum C-reactive protein (CRP) (10.14 mg/dL), IL-6 (111.69 pg/dL), and vascular endothelial growth factor (VEGF) (202.57 pg/dL) levels. Immunologic studies showed antinuclear antibody 1280-fold (speckled type); however, all specific autoantibodies were negative. Cytomegalovirus antigenemia assay and Epstein–Barr virus (EBV) DNA were also negative. An examination with 18F-fluorodeoxyglucose/positron emission tomography-computed tomography (18F-FDG/PET-CT) showed multiple lymphadenopathy with increased fluoro-2-deoxy-d-glucose (FDG) uptake (Fig. A). In addition, FDG accumulation was observed in her joints (Fig. A). Although no erosion was detected by the X-ray in the hands and feet, MRI revealed active synovitis and tenosynovitis in the right hand (Fig. B). MSUS assessment of the hands, elbows, and ankles showed synovial thickening with remarkable PD signals (Fig. C). Left axillary lymph node biopsy revealed blood vessels at the atrophied germinal center along with the accumulation of CD3+ T cells, CD20+ B cells, and CD138+ plasma cells consistent with CD (Fig. ).
We made a diagnosis of iMCD on the basis of international, evidence-based consensus diagnostic criteria.[ We excluded infection, malignancy, and autoimmune disorders that can mimic iMCD. The disease severity in this patient was classified as mild based on the criteria proposed in Japan.[ The patient's findings did not fulfill the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA.[ Accordingly, we initiated 15 mg/day of prednisolone (PSL) in mid-June 2018, and it reduced the arthritis, fatigue, fever, and lymphadenopathy as well as normalized the levels of Hb, albumin, and CRP. At the time of writing this report, we tapered the PSL to 7.5 mg/day, and the patient's remission has been maintained for >4 months. The clinical course of the patient has been shown in Figure . We evaluated her disease activity based on the recently proposed CHAP score.[ We investigated her serum cytokine levels at diagnosis before PSL initiation. Her IL-6, IL-17, and CXCL10 levels were higher than those of healthy controls; however, the tumor necrosis factor alpha, VEGF, and fractalkine levels did not show such a trend (Fig. ). |
pmc-6504299-1 | A 35-year-old man admitted to our hospital due to acute kidney disease (serum creatinine increased to 229 μmol/L from 132 μmol/L in <3 months previously). Regarding the patient's medical history, he underwent a surgical replacement of the whole aortic arch and stent trunk 6 years ago, and was diagnosed to have hypertension and diabetes since then. He had intermittent fever (38–39°C) in the last year. Laboratory investigations revealed the following alterations, including raised C-reactive protein, raised procalcitonin and gram-negative bacteremia of Pseudomonas aeruginosa. He received 3 cycles of long-term (7–9 weeks per cycle) intravenous antibiotics (including 1st cycle of piperacillin/sulbactam for 2 months, 2nd cycle of meropenem for 7 weeks, 3rd cycle including meropenem 2 weeks, piperacillin/sulbactam + levofloxacin 4 weeks, ceftazidime 3 weeks) in local hospital along the past year. Although his symptoms resolved rapidly with intravenous infusion of antibiotics and blood cultures repeatedly showed negative during therapeutic regimen; he had recurrent bacteremia of the same strain isolated within a couple of days after antibiotics withdrawal. At the end of the 3rd cycle of intravenous antibiotics, it was observed that he had decreased renal function, microhematuria and proteinuria of nephrotic range. Urinalysis showed protein 3+ and urinary occult blood 3+ (200–250/high power field) with dysmorphic erythrocytes; urinary protein excretion was 6.6 g/d (previous urinalyses had been unremarkable). Further workup showed increased immunoglobin (Ig) G 25.10 g/L (7.23–17.85) but normal IgA, IgM, complement C3, C4. And antistreptolysin O, rheumatoid factor, circulatory immune complex, antineutrophil cytoplasmic antibodies, antiglomerular basement membrane antibodies, antinuclear antibody, antiextractable nuclear antigens antibodies, antiphospholipase A2 receptor antibodies, cryoglobulin, and immunofixation electrophoresis were all negative. He presented transient gross hematuria under no obvious predisposing causes and then received renal biopsy.
Histologic examination of a renal biopsy sample (Fig. A–D) showed 28 glomeruli, 1 was globally sclerotic, and the nonsclerotic glomerular segments had foci of increased mesangial matrix and increased mesangial cells, including 10 cellular, 2 small cellular, and 1 small cellular fibrous crescents formation; there was no duplication of basement membranes. Immunohistology showed positive mesangial staining for IgM, albumin, whereas IgA, IgG, C1q, C3, and fibrin(ogen)-related antigens were negative. The cortex and outer medulla had acute tubulointerstitial damage with renal tubular epithelial vacuole degeneration, multiple brush bristles off, and multifocal atrophy; interstitial matrix expansion and focal interstitial infiltrate of lymphoid and mononuclear cells, plasma cells, neutrophils, and eosinophils. And arteriole hypertrophy was observed. Congo red reaction was negative. Electron microscopy showed increased matrix and segmental subendothelial and mesangial osmiophilic deposits in mesangial regions. These findings indicated focal mesangial proliferative glomerulonephritis with immune-complex-mediated crescentic formations as well as tuberous diabetic sclerosis.
18F-fluorodeoxyglucose/positron emission tomography–computed tomography (18F-FDG/PET-CT) showed multiple foci of increased metabolic activity at the site of aortic graft (Fig. E, F). We made a diagnosis of immune-complex-mediated crescentic glomerulonephritis triggered by chronic aortic graft infection with P aeruginosa.[ Due to special appearance and family history of sudden cardiac death, a whole-genome sequencing was taken and a TGFBR2 c.1133G>T mutation was observed, which was reported to be associated with Loeys–Dietz syndrome.
Antimicrobial susceptibility test showed multidrug resistance including all the previous antibiotics taken. The only susceptible drugs included amikacin, gentamicin, levofloxacin, and ciprofloxacin. He 1st took intravenous fosfomycin sodium combined with levofloxacin. But he cannot stand by fosfomycin because of heavy vomiting. So he received intravenous ciprofloxacin (0.4 g, q 12 hours) combined with amikacin (0.2 g, q 12 hours for 4 weeks). After 8 weeks of antibiotics of sensitive antibiotics, blood cultures remained negative and C-reactive protein decreased to normal. But his renal function did not recover, and 2 weeks of small dose of steroid (prednisone 15 mg/d) was taken. His serum creatinine returned to normal range (Fig. ).
He continued oral antibiotics of fosfomycin sodium (1.5 g qd) and ciprofloxacin (0.2 g bid) in the following year. Up to date, the patient has been followed up for 1 year. More recent urinalysis showed negative protein and urinary blood. |
pmc-6504319-1 | A healthy 31-year-old woman, G4P3, presented to our hospital during her 4th pregnancy. She had a history of 3 CSs in 2011, 2013, and 2017 in other hospitals. She was 38+3 gestational weeks. Abdominal ultrasonography showed that PPP in the lower edge of the placenta was close to the cervix, and it was suspected to be combined with PA. Placental magnetic resonance imaging (MRI) showed PPP and PA in the anterior inferior uterine incision scar site (Fig. ). A routine blood examination showed that her Hb level was 72 g/L and her hematocrit was 22.7%. The blood bank supervisor checked the patient's ABO, Rh, and antibody status and found that she had positive antibodies to red blood cells. Because the patient had PPP and PA, life-threatening bleeding could occur during CS. Therefore, 3 units of leukocyte-depleted red blood cell suspension were intravenously infused. This leukocyte-depleted red blood cell suspension did not contain positive antibodies to red blood cells. There was no blood transfusion reaction during this process.
On the 2nd day after allogeneic blood transfusion, the patient did not have any emergency bleeding symptoms, but her Hb level was 68 g/L. Hemolysis was suspected, and thalassemia and hemolysis-related indices were urgently examined. The patient had intermittent established labor. Therefore, the obstetrician decided to terminate the pregnancy immediately. After obtaining consent from the patient, bilateral internal iliac artery (IIA) balloons were placed in her IIA before CS. The patient was then immediately transferred to the operating room. At the time of PTUI CS, the results of hemolysis and thalassemia indices were unknown.
When the patient entered the operating room, blood pressure was 117/74 mm Hg and her heat rate was 84 beats/min. A radial arterial catheter was placed to monitor continuous arterial blood pressure and for measurement of the acid/base status. Her Hb level was 65 g/L. Intraoperative cell salvage, which collects, processes, and returns the woman's own blood lost during surgery, was used. A vertical abdominal incision was made under general anesthesia. Obvious distension of the lower anterior wall, and large blood vessels and the placenta penetrating through the anterior uterine wall were observed during laparotomy (Fig. ). After confirming the location of the placental margin according to preoperative MRI results, the first transverse incision was made near the uterine fundus and above the upper border of the placenta, without transecting the placenta.
A healthy male infant was delivered from the first incision, and he weighed 2830 with a height of 50 cm. The newborn's Apgar scores were 10 and 10 after 1 and 5 minutes, respectively. The placenta remained in the uterus. Bleeding from the first incision was minimal and was easily controlled by blood vessel ligation. After delivering this neonate, the inhalation concentration of sevoflurane was increased to 2.0 to 3.0 minimum alveolar concentrations to achieve complete uterine relaxation. According to the degree of uterine relaxation, intermittent venous injection of 100 μg nitroglycerin was performed to maintain uterine relaxation. If blood pressure greatly decreased, intravenous injection of 100 μg phenylephrine was performed to raise blood pressure. The first uterine transverse incision was closed by a rapid, continuous, double-layer suture after ligation of the umbilical cord. Bilateral small openings were made in an avascular area of the ligament at the level of the cervix. A narrow rubber tourniquet was then passed through both openings and tied tightly below the cervix to restrict uterine blood flow. The uterine body under the first fundus incision was also tied tightly by another rubber tourniquet to prevent bleeding from this incision. At the same time, prepositioned bilateral occlusion balloons of the IIA were then filled to completely obstruct the blood supply. The inhalation concentration of sevoflurane was decreased to 1.0 minimum alveolar concentration. A second transverse uterine incision was made in the lower segment of the uterus, and the placenta was manually removed under direct observation. Wedge resection of the thin uterine wall at the PA site of the anterior uterus was performed (Fig. ). The bilateral IIA balloons and the narrow rubber tourniquet for restricting blood flow to the uterine cervix and uterine fundus were then loosened. No bleeding occurred, and the second transverse uterine incision was closed using interrupted sutures. Because the patient already had 3 children, a bilateral tubal ligation operation was performed as strongly requested by the patient. In the whole operation, the total blood loss was estimated to be 1.3 L, and she was transfused 462 mL of recycled red blood cells processed with a leukocyte depletion filter. The lowest recorded Hb level was 54 g/L with a hematocrit of 16%. However, at the end of the operation, her serum hemoglobin level was 63 g/L, hematocrit was 19%, and the activated partial thromboplastin time was normal. |
pmc-6505046-1 | A 21-year-old woman was referred with aggression, irritability, talkativeness, decreased need to sleep, and racing thoughts without psychotic features.
Her symptoms commenced about 3.5 years ago. She had two prior psychiatric hospitalizations 1.5 and three years ago. The first episode was depression and she had history of two suicidal attempts in the depressed phase. In the second episode, she experienced mania with psychotic features. Because of drug noncompliance after the second episode, a long acting antipsychotic agent (Flupentixol Decanoate) was prescribed for her once monthly. The latest injection was 1.5 months before admission, but she stopped taking Biperiden (4mg/day) and lithium carbonate (900mg/day) since five months ago.
She had a family history of major depressive disorder in her mother and elder sister. She had not any medical comorbidities or history of brain trauma or autistic disorder. Moreover, she had no history of benzodiazepine or alcohol withdrawal.
Laboratory data at the admission time were within normal range except for vitamin B12 level which was in the range of severe deficiency (as the result of vegetarianism). The brain neuroimaging (MRI) revealed no abnormality.
At admission, she had non-cooperative attitude, irritable mood with congruent affect, and pressure of speech without any hallucinations or delusions. She was well-oriented. Her vital signs were within normal levels. In medical examination, she had no tremor, rigidity, or any other extra pyramidal signs.
Drug regimen included lithium carbonate up to 1200 mg/day with 1 mg/dL of serum level, Quetiapine up to 600 mg/day, and Biperiden up to 4 mg/day. Within 3 weeks of non-responsiveness, lithium carbonate was tapered and discontinued within a week. The rest of the medications continued. Then, bitemporal ECT was given with energy level of 25% every other day. Duration of seizures was between 22 to 45 seconds. Anesthesia was induced by Atropine 0.5 mg IV, Succynil choline 25 mg IV, and Thiopental sodium 150 mg IV. The reason for the ECT was non-responsive to the medications, and the patient's family insisted for treatment as soon as possible due to fear of possible consequences of mania for the patient.
She developed some negativism after the fourth session of ECT, and after the fifth session, she developed full catatonic state including waxy flexibility, posturing, negativism, mutism, and echolalia.
Her vital signs were normal and she had not any autonomic dysfunction and extrapyramidal signs. The patient had no history of catatonia or neuroleptic malignant syndrome.
ECT and other psychotropic drugs were discontinued as soon as possible, and lorazepam was prescribed and increased up to 4mg/day twice a day.
The fulminant catatonia resolved after 4 days of treatment, and lorazepam was tapered after remission. Because of non-responsiveness to other antipsychotic agents, clozapine was started and its dose was escalated to 200 mg/day during 25 days until the patient’s discharge. After discharge, there was no sign of recurrence of catatonia in the follow- up sessions.
Informed consent was obtained from the patient for presentation. |
pmc-6505083-1 | A 54-year-old woman with symptoms of numbness and weakness in the right leg with no obvious cause presented to the field hospital. The diagnosis was the possibility of metastatic tumour after head CT and MRI examination. Pathological findings at another hospital suggested demyelinating disease. The patient was treated with hormone drugs in the field hospital and her symptoms were relieved. But the numbness in her right leg was aggravated, and symptoms of dizziness and nausea appeared two months later. The patient was eventually admitted to the Department of Nerve Infection and Immunology at Tiantan Hospital for concentric sclerosis. The patient had a history of hypertension, hyperthyroidism, and mammary gland hyperplasia but no history of diabetes, heart disease, hepatitis, tuberculosis, or drug allergy.
Physical examination after admission found a decrease in her calculation capacity. She had instability of pointing at her nose with her right finger and the tibial experiment with her knee in the nervous system examination. She had no other obvious abnormalities.
Laboratory examination after admission found that her leukocyte level in a routine blood examination was 13.52 × 109/L. Her glucose (2.93 mmol/L), sodium (124 mmol/L), and chlorine (87 mmol/L) levels were decreased. Her fibroproteinogen (1.62 g/L) level was decreased. A routine CSF examination revealed her CSF had a yellow and clear appearance, and the total number of CSF cells was 514/μl. The number of leukocytes was 14/μl. Her CSF protein was high (82.54 mg/dl), and her 24-h IgG intrathecal synthesis rate was increased (13.54). The IgG oligoclonal band of her CSF was negative. Her cytokine interleukinin-10 level was 641.00 pg/ml .
The patient’s cytomegalovirus IgG of the CSF was positive. Neuronal antigen spectrum antibody IgG (CSF and blood) were negative. Tumour markers (female) were negative. Autoimmune antibody tests and protein electrophoresis were normal. The result of a CSF culture indicated Bacillus (suspected contamination). CSF gram stain, acid fast stain, and ink stain were negative (Tables , , , , ).
Colour Doppler ultrasound of the patient’s abdomen, urinary system, thyroid, lower extremity veins, and superficial lymph nodes were performed, with no abnormal findings. PET-CT indicated no metastatic tumour lesions.
Head MRI enhanced scanning demonstrated multiple abnormal signals in the double frontal cortex, subcortical, basal ganglia, temporal lobe, and callosum. Inflammatory demyelinating disease was more likely, and lymphoma was not excluded. Abnormal signals of the left parietal lobe were demonstrated after biopsy, and there was an ischaemic infarct in the patient’s right cerebellar hemisphere (Fig. ).
CSF cytology conducted in the laboratory at Tiantan Hospital showed that a group of cells were suspected lymphoma cells. They had larger bodies and irregular nuclei, visible nucleolus, abundant cytoplasm, and deep staining, and this type of cell accounted for 11% (Fig. ). We promptly communicated with the clinic, and the doctors were very excited about the valuable diagnostic basis of this difficult case.
According to the CSF cytology results, the patient’s clinicians immediately prescribed flow cytometry and CSF DNA sequencing. CSF flow cytometry showed that 14.86% of her cells (129 karyocytes) expressed CD38, CD22, CD19, CD20, kappa, CD79b, CD180, CD54, and CD44. Some cells were considered malignant monoclonal mature B cells. They expressed K167 (40%), CD9, and CD200 and did not express CD56, CD2, CD7, CD3, CD4, CD8, CD138, CD30, lambda, FMC7, CD103, CD25, CD11C, and CD34 (Fig. ). CSF DNA sequencing demonstrated that the IGH and IGL clonal rearrangement was negative and the IGK clonal rearrangement was positive (Fig. ).
Combined with CSF cytology, flow cytometry, and DNA sequencing, the patient was diagnosed with primary central nervous system lymphoma (diffuse large B cell lymphoma) and transferred from the Department of Nerve Infection and Immunology to the Department of Haematology for further treatment.
In the Department of Haematology, the initial treatment was rituximab combined with a chemotherapy regimen (R-MAD). On the second day, the patient was administered a lumbar puncture and intrathecal injection of 50 mg cytarabine and 5 mg of dexamethasone, and then the routine, biochemical, and cytological examinations were repeated. CSF cytology showed that the lymphoma cells had decreased to 1%. On the third day, the patient had a clear state of mind but her spirit was weak, and there was no nausea and vomiting and no obvious adverse reactions to chemotherapy. |
pmc-6505100-1 | On March 11, 2016, a 64-year-old mestizo man with a history of benign prostatic hyperplasia and use of an indwelling catheter presented to our emergency department with urinary retention. Cystoscopy revealed intravesical clots and obstructive bilobar prostate. Following the procedure, the patient exhibited signs of systemic inflammatory response syndrome and pathologic urinalysis. Therefore, antibiotic therapy with ampicillin/sulbactam was initiated without improvement in the clinical features. The urine culture report showed the presence of carbapenem-sensitive Pseudomonas aeruginosa and Enterobacter cloacae. Therefore, the therapy was subsequently escalated to meropenem (1 g every 8 h). The patient presented with clinical deterioration and ventilatory failure and was referred to the ICU for orotracheal intubation. He also developed cardiopulmonary arrest, which required basic and advanced resuscitation techniques for 11 min with subsequent sinus rhythm. On physical examination, the patient was under sedation, tachycardic, and hypothermic with evidence of purulent urethral discharge, and he required vasopressor support and sedoanalgesia. He had multiple organ dysfunctions due to urinary and pulmonary sepsis with the identification of carbapenem-resistant Klebsiella pneumoniae in the blood and lower respiratory tract secretions. The antibiotic therapy was adjusted to colistimethate (90,000 IU/kg) divided into three daily doses, doripenem (1 g every 8 h), and fosfomycin (4 g every 6 h). The patient initially progressed toward improvement, but 72 h later, he presented with new signs of inflammatory response. Therefore, a new blood culture was performed, revealing a carbapenem-resistant A. baumannii isolate (minimum inhibitory concentrations [MICs] ≥ 16, ≥ 16, and ≥ 8 μg/ml for imipenem, meropenem, and doripenem, respectively) that was also resistant to gentamicin (MIC ≥ 16 μg/ml), ciprofloxacin (MIC ≥ 4 μg/ml), and colistin (MIC 16 μg/ml) and sensitive only to tigecycline (MIC 1 μg/ml). Following this test, tigecycline administration was initiated (100 mg every 12 h), and colistimethate was suspended, with fosfomycin and doripenem continued until the completion of 14 days of treatment. Nevertheless, due to the persistent systemic inflammatory response on day 10, rifampicin (600 mg/day) and ertapenem (1 g every 12 h) were initiated for pharmacological synergism until day 14. With the prescribed antibiotic therapy, the patient improved in terms of infection, with an absence of fever and decreased leukocyte count. New blood and urine cultures were done, with negative results.
Molecular typing confirmed the genus and species of the isolate as A. baumannii (excluding other species of the Acinetobacter genus), as well as the presence of the blaOXA-23 gene (associated with carbapenem resistance). The isolate belonged to the sequence type (ST) 944, which has also been described in isolates identified in Russia, Italy, and the United States. Studies have identified intrahospital outbreaks of colistin-resistant bacteria with predominant genotype according to multilocus sequence typing was ST-258, ST11, ST273, and ST15 for K. pneumoniae; ISAba1 in P. aeruginosa, and pmrA1 and pmrB genotype ST94 for A. baumannii []. There are few reports on the resistance mechanisms associated with resistance to colistin in A. baumannii, the most important one being that related to loss in the production of lipid A of lipopolysaccharide. This loss has been associated with mutations in the pmrAB and lpxACD operons, lpxK, or the ISAba11 insertion [, ]. The sequencing of these two operons in the A. baumannii isolate identified two nonsynonymous mutations (H31P and I215M) in the lpxC gene from the ATCC 19606 strain and another nonsynonymous mutation (A178G) in the pmrC gene from the ATCC 17978 strain [–]. None of these mutations has previously been reported in colistin-resistant strains. Although they have been found in the A. baumannii isolate, their possible association with resistance should be confirmed experimentally. |
pmc-6505103-1 | The 44-year-old male acute myeloid leukemia (AML) patient received an unmanipulated graft from an unrelated donor (CMV D−/R+) after conditioning with the FLAMSA protocol. The patient received acyclovir (ACV, 400 mg twice per day) continuously, except between days + 43 to + 70 and day + 110 to + 145 (summarized in Fig. ). For maintenance of immunosuppression, the patient received cyclosporine A per os (measured blood concentrations 180–220 μg/L), mycophenolate (360 mg twice daily), and prednisolone.
It was planned to start LMV prophylaxis directly after the transplantation. However, due to a delay in delivery, administration of LMV could only be initiated at day + 34, under the assumption that CMV viral load was still below detection limit (50 IU/ml in serum). The compound was given at 240 mg once per day per os, along with cyclosporine. In retrospect, it turned out that the virus DNA load at the last check on day + 28 was 190 IU/ml in serum. Over the next 8 days, increasing CMV loads were measured up to 39.600 IU/ml. Therefore, letermovir treatment was discontinued and the patient was switched to valganciclovir (valGCV, 900 mg twice per day) at day + 42. Treatment was maintained for 4 weeks until CMV DNA was negative. At this time, the patient suffered from an intestinal graft-versus-host disease (GvHD) and a mucositis. Therefore, prednisolone was administered at day + 46 for 7 days with 10 mg and then was reduced to 1 mg until discontinuation at day + 82.
As neutropenia occurred during valGCV therapy, stimulation with G-CSF was necessary. After discontinuation of valGCV, neutropenia was resolved and LMV secondary prophylaxis was started at day + 70 with 240 mg once per day. At this time point CMV DNA was not detectable. At day + 80, mycophenolate was discontinued. For 4 weeks, CMV DNA remained undetectable or at the limit of quantitation of 125 IU/ml. At day + 97, tapering of cyclosporine A was initiated. However, several days later, the patient failed to maintain virologic suppression. CMV viral loads rapidly increased to 236.400 IU/ml in serum samples, between days + 104 and + 110. In order to avoid neutropenia, valGCV treatment with a reduced dosage of 450 mg twice per day was initiated at day + 110. Concomitantly, LMV dosage was increased to 480 mg per day. During the next 4 weeks, CMV viral loads decreased to 1.200 IU/ml. ValGCV treatment, which meanwhile necessitated daily stimulation with G-CSF, was discontinued.
However, CMV DNA levels increased up to 33.000 IU/ml during the following 2 weeks. Therefore, genotyping of the CMV terminase UL56 as well as the other relevant genes (UL97 kinase, viral polymerase UL54, and UL89) was initiated. Thereby, a mutation corresponding to amino acid 325 (C325Y, cytosine at amino acid 325 to tyrosine) of UL56 was detected (see Fig. ). This mutation is associated with a high resistance to LMV in vitro []. Therefore, LMV was discontinued at day + 167.
No further mutation was detected. Retrospective analysis revealed that the UL56 mutation C325Y was already present at day + 117, within 6 weeks after the start of the second letermovir administration. Unfortunately, no other patient specimens were available in order to further elucidate the time point of emergence of the mutation.
Since then CMV DNA loads remained at a low level of 1300 to 2500 IU/ml. Due to the lack of clinical symptoms and increasing CD4 T-cells since day + 145, no further anti-CMV therapy was carried out.
Until today, the patient is clinically stable and participates in a professional reintegration. |
pmc-6505115-1 | A 58-year-old man was hospitalized for haemorrhoid surgery. His medical history featured only hypercholesterolaemia.
On day 1 after surgery, he developed fever and symptoms of prostatitis, with no digestive symptoms. Following blood and urine cultures, antibiotherapy (ofloxacin and gentamycin) was initiated. Platelet count was 100 G/L (normal before surgery), haemoglobin (Hb) was normal (14.5 g/dL). Renal function was normal (serum creatinine = 1.02 mg/dL).
Urine and blood cultures came back positive for Escherichia coli and ofloxacin was continued. No E.coli was found in the stools (culture and PCR).
On day 4, platelet count decreased to 27 G/L, without anaemia, and creatinine rose to 1.75 mg/dL, but the patient had urinary retention.
Day 6, although the infection was under control and the patient had remained haemodynamically stable throughout (blood pressure 120/62 mmHg), he developed acute kidney injury (AKI) with anuria (creatinine = 7.36 mg/dL) and neurological signs which included confusion, hallucinations, anterograde amnesia, static cerebellar syndrome and transient motor deficit of the left lower limb. The renal CT-scan was normal, as was cerebral magnetic resonance imaging (MRI). Laboratory tests showed: Hb = 11.8 g/dL, haptoglobin = 1.53 g/L, LDH = 2615 U/L (upper limit 480 U/L), platelet count = 61 G/L.
This renal and neurological presentation was initially attributed to sepsis and possible drug toxicity (antibiotics). Haemodialysis was started and antibiotherapy modified to ceftriaxone.
On days 9–12, the patient’s neurological state worsened: he presented seizures, controlled using anti epileptic treatment. The spinal tap was normal. At this point Hb had dropped to 8 g/dL, LDH remained elevated (1265 U/L) and schistocytes 3% were detected. Platelet count, however, normalized (250 G/L). ADAMTS13 activity was normal (38%, with FRETS-VWF73 technique), thus excluding a diagnosis of TTP. Antinuclear antibodies and ANCA were negative.
A hypothesis of HUS associated with “non-intestinal” STEC infection was made.
An initial complement work-up revealed no abnormalities (Table ).
A kidney biopsy, performed on day 15, confirmed the diagnosis of HUS. Light microscopy showed 13 permeable glomeruli with endothelial cell swelling, widening of the subendothelial space, and double contours of the glomerular basement membrane. Fibrin and platelet thrombi were observed in glomerular capillaries. Images of regenerating tubular necrosis were also observed. An immunofluorescence study revealed no significant immune deposits (Fig. ).
Haemolysis subsequently disappeared and the patient’s neurological state improved. Although urine output increased, the patient remained on dialysis.
While waiting to identify the type of E. coli involved, we were unable to exclude a diagnosis of non-intestinal STEC-HUS. In view of the favorable outcome, the patient did not receive any plasmatherapy, or complement inhibitor. However, we were able to discontinue dialysis after 1 month as renal function improved.
When testing for anti-LPS antibodies in serum was repeated 3 weeks after disease onset, no E.coli typically associated with HUS in France was found (detection of IgM and IgA (‘line-blot’) anti-LPS antibodies in the serum, for serogroups O26, O55, O91, O103, O111, O128, O145, O157). Moreover, screening for virulence factors of the E.coli found in blood cultures came back negative (stx1 and stx2 gene amplification negative; eae and ehxA gene amplification negative; fyuA, hlyC, sfa/foc, papC, iucC, papGIII, cnf1, papGII, iroN, vat, clbB genes negative).
After 3 months, serum creatinine was 2 mg/dL and proteinuria was 0.4 g/day. After 1 year, serum creatinine remained stable at 1.5 mg/dl, with normal blood pressure and clinical state. No recurrence has been observed over a 3 year period.
Screening for rare variants in complement alternative pathway genes was performed (Technique: EUrenOmics NGS panel) and showed the presence of a heterozygous variant in the gene encoding complement factor H (p.Val215Ile; c.643 G > A). This variant is located in the N-terminal domain of the protein (SCR4) and is not present in the ExAc data base (). |
pmc-6505124-1 | This is a 6-year old girl, second daughter from non-consanguineous and healthy parents. She was born by programmed caesarean delivery at 38 weeks of gestation, after an uneventful pregnancy. Birth parameters were normal: weight 97th, length 54th, head circumference 80th percentile. Postnatal adaptation was normal; APGAR scores were 9 and 10. Congenital hip dysplasia was treated with a harness. She was first referred to medical attention at 11 months for a progressive delay of psychomotor milestones. Neurological examination confirmed motor and language delays with only head control achieved, impaired social interaction, muscle hypotonia and brisk tendon reflexes. Routine blood test including thyroid hormones, serum creatine kinase, standard karyotype, cardiological and abdominal ultrasound evaluation were all normal. Routine EEG revealed increased background theta-delta activity with posterior spike-like elements, particularly in the right occipital area.
At 16 months, after global psychomotor training, social skills and language had improved, though she was not able to sit unsupported. Mild facial dysmorphic features were also noticed (hypertelorism, epicanthal folds, depressed nasal bridge, puffy hands and feet). Neurophysiological examination and laboratory investigations, including organic aciduria, serum aminoacid and lactate levels, were unremarkable.
At 32 months, developmental delay, axial hypotonia with limb hypertonia, brisk tendon reflexes and ankle hypomobility were prominent features with evidence of further regression. Brain MRI showed corpus callosum hypoplasia and cerebellar cortex atrophy (not shown). Array CGH and serial metabolic screening resulted normal.
Follow-up MRI at 47 months, revealed atrophic progression of the cerebellum with T2-FLAIR hyperintensities of cerebellar white matter and dentate nuclei (Fig. .a-b). MR spectroscopy of corresponding cerebellar white matter alterations showed increased lactate and decreased N-acetilaspartate peaks. Head circumference decreased up to the 10th percentile. Despite no seizures had ever been reported by parents or observed during hospitalizations, standard and sleep-deprived EEGs were significant for spike-waves involving temporal and occipital areas.
At about 5 years, neurological condition worsened. The patient could barely speak in sentences with simple words, had a limited broad-based gait with bilateral support; bilateral spasticity in upper and lower limbs was present. A skeletal muscle biopsy revealed partial reduction of respiratory chain enzyme complexes I + III (0.13 mmol/min/gr of tissue, normal range 0.65–1.50). Blood DNA from the proposita was analysed using a customized targeted resequencing panel (MitoChip) able to investigate the coding regions of 1172 nuclear genes encoding the “MitoExome” []. Using this strategy we identified the homozygous c.1100C > T (p.Thr367Ile) in VARS2 (NM_001167734). The mutation was confirmed by Sanger sequencing and segregated in heterozygosity in healthy parents.
At last follow up (age 6 years), the patient manifested sporadic and transient myoclonic movements of the right arm, proven to have a subcortical origin by EEG recording. She is currently able to walk with bimanual support and to formulate complex sentences; neither seizures nor dysphagia are reported. Myoclonic jerks are rare. She is attending school with good social skills. Moreover she is undergoing daily global psychomotor training. She is currently under Coenzyme Q10 (11 mg/kg/day) and Riboflavin (9 mg/kg/day) supportive antioxidant therapies. |
pmc-6505124-2 | This is a 5-year old girl, the only child from non-consanguineous and healthy parents. She was born after 41 weeks of uneventful gestation by natural delivery. Postnatal adaptation was normal. Due to congenital hip dysplasia, she was treated with a harness. At 12 months, the patient could not walk autonomously and was only able to sit unsupported. At 2 years, neurological examination revealed nystagmus with alternating strabismus, brisk tendon reflexes, global hypotonia and impaired coordination. Gait was possible only for a few steps with bimanual support; social skills and language appeared normal for age. Facial dysmorphisms were also recorded, and included microphthalmia, hypertelorism, strabismus, tilted ear axes and fleshy lips. Routine laboratory investigations in blood were uninformative, except for an increased serum lactate. Cardiological evaluation, abdominal ultrasound and genetic testing (standard karyotype, array CGH) were normal. Standard EEG showed modest non-epileptic abnormalities in both frontotemporal regions. Brain MRI at 2 years showed a mega-cisterna magna with signs of cerebellar atrophy (Fig. .c). At age 3, the patient underwent a global psychomotor training. After 9 months, she developed involuntary movements with recurrent paresis of the upper right limb. EEG showed sleep-driven spike-wave abnormalities in bilateral temporal regions. A successful treatment with Clobazam (10 mg/day) went on for 1 month.
Follow-up brain MRI performed at age 4, displayed cerebellar atrophy and vermis hypoplasia with normal spectroscopy (not shown). At 4.5 years, she complained of secondarily generalized tonic-clonic seizures with intensification of EEG epileptic abnormalities and was treated with Levetiracetam 300 mg/day (20 mg/kg). Severe psychomotor and social regression occurred. Exome sequencing using reported methodologies (Diodato D et al. 2014) revealed the homozygous c.1100C > T (p.Thr367Ile) mutation in VARS2. She is currently unable to sit and to speak. Due to swallowing difficulties she recently underwent percutaneous endoscopic gastrostomy. She is under antiepileptic polytherapy (Levetiracetam 20 mg/kg/day; Clonazepam 0.01 mg/kg/day) together with supportive antioxidant treatment (Q10 Coenzyme 11 mg/kg/day and Riboflavin 9 mg/kg/day). |
pmc-6505200-1 | A one-year-nine-month old Chinese girl with symptoms of hearing loss and retrogression of speech and movement since one-year-old presented in our out-patient service. The patient was responsible to teasing, and her neck stood firmly at the age of 5 months. She was able to flip over her body at the age of 8 months, responded when her name was called, and was able to call mom and dad at the age of 9 months. However, her motor development lagged behind her peers obviously. She was not able to sit and crawl independently at one-year-old. Since then, the patient gradually lost her response to surroundings and had lack of facial expression and hypotonia, especially weakness in upper limbs, including loss of hand agility and lack of grabbing. Other symptoms included choking when drinking and swallowing difficulty, but seizure was not observed. Her body weight decreased from 10.5 kg to 8 kg after the symptoms manifested. She started holding her breath for 1–2 min frequently after crying, starting at the age of 10 months. Cyanotic breath holding spells (BHS) occurred on an average of 10 times/day. She was the first child of non-consanguineous parents. The first and second pregnancies were ceased by her parents, and the 3rd pregnancy was aborted because the embryo stopped developing. She was born at 32+ 6 weeks of gestation through cesarean section because her mother suffered from pregnancy-induced hypertension. Her birth weight was 1.36 kg, and her newborn hearing screening result was unremarkable. When she came to the clinic at one-year-nine-month, her height was 77 cm, her weight was 8 kg, and her head circumference was 45 cm, all lagging behind children of the same age. She could only control her head, and she showed poor visual fixation and sound tracking. Physical examination showed generalized weakness, especially the upper extremities, hypotonia of limbs, weak gag reflex, absent of patellar tendon reflex, and negative bilateral Babinski sign. Ammonia, serum lactic acid, hepatorenal function, microelements, and serum amino acids were normal. Acylcarnitine profile showed mild abnormalities including mild elevation of octanoyl carnitine (C8): 0.33 μmol/L (0.01–0.30 μmol/L) and decanoyl carnitine (C10): 0.50 μmol/L (0.01–0.35 μmol/L). Other acylcarnitine species were within the normal ranges. Her urine organic acid analysis showed mild elevated pyruvic acid and lactic acid.
Magnetic resonance imaging (MRI) of the brain showed no contrast and visual-evoked response. Video electroencephalogram and echocardiography were normal. Electromyogram was neurogenic with fibrillation activity. Nerve conduction studies showed denervation without sensory response of the sural and median nerves but normal motor velocities. Brainstem auditory-evoked responses revealed severe sensorineural hearing loss. The ophthalmologic examination was normal. With the consent of the child’s parents, genetic testing was performed. No variant was found in the SMN (survival motor neuron) gene, which encodes survival motor neuron protein. Her karyotype analysis was normal. |
pmc-6505212-1 | 52 y/o female with no significant past medical history initially presented with left lower quadrant abdominal pain. Family history includes lung cancer in brother at age 62 years who had a risk factor of chronic smoking. Paternal grandmother had bilateral synchronous breast cancer at the age of 80. Grandfather had prostate cancer at 79. No family history of gastrointestinal or ovarian cancer was reported. Pedigree chart for patient’s family history of cancer is shown below (Figs. and ). Physical examination was normal. CT scan of the abdomen showed an obstructed rectosigmoid mass. Colonoscopy showed recto sigmoid mass 4.5 × 6.5 cm which was 18 cm from the anal verge. Biopsy revealed a moderately differentiated adenocarcinoma. A CT scan of the chest and abdomen did not show evidence of distant metastases. The patient underwent laparoscopic rectosigmoid and local lymph node resection with a left end colostomy. Pathology showed an invasive, moderately-differentiated adenocarcinoma with infiltration beyond the muscularis propria into subserosal tissue. There were high risk features, including lymphovascular, perineural invasion along with six of twenty-eight lymph nodes positive for adenocarcinoma. Initial surgical specimen after colectomy was sent for analysis with next generation sequencing test. Tumor mutations included BRIP1 P619Fs*20: TP53 S2151, splice site 783-2A > G: CDK8 amplification was equivocal and APC E 1295*. Lynch syndrome screen by immunohistochemistry (MLH1, MSH2, MSH6 and PMS2 proteins) showed normal expression in pathological tissue. There were no reportable alterations in KRAS, NRAS, and BRAF. The patient had colon cancer at the relatively young age of 52 with no family history. The patient requested an evaluation of possible hereditary predisposition. Initial testing with a commercially available 17 gene colon cancer risk panel was negative. Additional germline testing for BRIP1 gene mutation was proposed based on high allele frequency of BRIP1 mutation in tumor tissue. The patient was found to be heterozygous for the c.853_1854lnsG mutation located in coding exon 12 of the BRIP1 gene. No other germline mutations were identified with the panel testing used. She was staged as IIIB disease (pT3 pN2a M0). She was treated with twelve cycles of adjuvant chemotherapy FOLFOX (5-fluorouracil, leucovorin, oxaliplatin). Six months after finishing chemotherapy, the patient underwent laparotomy for planned colostomy reversal. She was found to have intraoperative findings of metastasis to the omentum and left the ovary. She was treated with HIPEC surgery (Hyperthermic intraperitoneal chemotherapy), omentectomy and bilateral salpingo-oophorectomy. She then received eight cycles of chemotherapy FOLFIRI (5-fluorouracil, Leucovorin, Irinotecan) for disease recurrence. The patient had another recurrence 1 year later with new pulmonary metastatic disease and pleural effusion. She was treated with six cycles of chemotherapy with FOLFOX and Bevacizumab and currently on maintenance 5-Fluorouracil and Bevacizumab therapy. |
pmc-6505212-2 | Sixty-two y/o female with a history of uterine fibroid, hysterectomy and salpingo-oophorectomy underwent screening colonoscopy which showed 4.9 × 3.4 cm circumferential mass in the proximal ascending colon. The patient did not have any gastrointestinal complaints of abdominal pain, constipation or blood in stools. Family history includes metastatic colon cancer in mother at age 77, maternal aunt diagnosed with colon cancer at age 50; another maternal aunt was diagnosed with uterine cancer in her 70’s. Two cousins on the maternal side had colon cancer at age 50. Pedigree chart for patient’s family history of cancer is shown below (Fig. ). Physical examination was normal. Biopsy of colon mass showed moderately differentiated adenocarcinoma. Staging work up revealed two liver lesions. She underwent laparoscopic right colectomy and partial hepatectomy. Surgical specimen after hemicolectomy was sent for next-generation sequence analysis. Genomic alterations identified include BRIP1 S988 fs: AKT1 E17K: mTOR E1799K: APC R1450: CREBBP S889: FAM123B R358: GNAS R201C: TP53 P177L and 4213Q. No reported alterations in KRAS, NRAS, and BRAF. Lynch syndrome screen by IHC (MLH1, MSH2, MSH6 and PMS2 proteins) was normal on the pathological tissue. The patient had a family history of colon cancer and wanted to be evaluated for gene mutations associated with hereditary cancer. Initial testing was done with commercially available 17 gene panel associated with colon cancer. Further germline testing for BRIP1 gene mutation was done based on high allele frequency of BRIP1 mutation in tumor tissue. This showed patient was heterozygous for c.2962deIT pathogenic mutation located in coding exon 19 of the BRIP1 gene. She was staged as IVA given metastatic liver disease. She was treated with twelve cycles of chemotherapy FOLFOX. Two years later she was found to have a recurrence with liver lesions on PET CT. She underwent laparoscopic resection of hepatic metastases followed by adjuvant chemotherapy with eight cycles of FOLFIRI. Repeat scans did not show any active disease. |
pmc-6505215-1 | Patient 1 (Fig. and Table ) is a 50-year-old male with moderately differentiated ICC staged at IIIb. He was admitted to the hospital in January 2016 due to upper abdominal pain. He had a history of hepatitis B for 10 years, and his Child-Pugh class was A. Magnetic resonance imaging (MRI) revealed a mass in the left outer lobe, which grew outward and invaded the diaphragm. The tumour marker carcinoembryonic antigen was elevated at 10.14 μg/L. He underwent left hemihepatectomy and hepatoduodenal ligament skeletonization on February 16, 2016. The tumour was 11 cm × 9 cm × 6 cm, and no lymph node metastases were found. Intraoperative radiotherapy was performed on the liver section using 9-mV photon beams with a single dose of 12 Gy, which could eliminate the residual tumour due to invasion of the diaphragm and the venous root of the liver. The tumour was found to be positive for cytokeratin 18 (CK18) and was negative for Arg-1, hepatocyte, glypican-3 (GPC-3), and CK7 in IHC analysis. The tumour proportion score (TPS) of the PD-L1 expression level was < 5% determined using monoclonal mouse anti-human PD-L1 clone (22C3) antibody by allred criteria, and the frequency of infiltrating CD8+ T cells was 10%.
Liver resection margin recurrence and abdominal lymph node metastasis were detected using MRI and positron emission tomography-computed tomography (PET-CT) after 11 months. MRI showed a marginal lesion of 4 × 1.5 cm in the left lobe of the liver, along with an enlarged hepatic hilar (1.6 × 1.5 cm) and retroperitoneal lymph nodes (5.2 × 3 cm and 2.8 × 2.6 cm). PET-CT scans also revealed abnormal hypermetabolic lesions in these locations.
Whole-exome sequencing (WES) was applied to the tissue resected after surgery, and the data were used to determine the presence of SNVs, indels, the TMB, copy number variations (CNVs), MSI status, and dMMR by bioinformatics methods. The TMB was determined to be 2.95 mutations/Mb, and a total of 25 non-synonymous mutations (NSMs) were detected in the whole genome, including 12 indels and 13 SNVs. This patient harboured only one clinically actionable mutation in FGF4, which amplified to reveal a copy number of 3.64. No SNVs were detected in MLH1, MSH2, MSH6, and PMS2 (Additional file ), suggesting pMMR, and the MSI was 0.01%.
The left hepatic lobe lesions and retroperitoneal left lymph nodes were treated with Cyberknife (52 Gy/4 F for 4 days) on February 4, 2017 and February 9, 2017, respectively. Tegafur and pembrolizumab were initiated 9 days apart. Tegafur chemotherapy was started at 40 mg twice a day every 3 weeks but was withdrawn due to development of thrombocytopenia and leukopenia after three cycles. Pembrolizumab was administered at 150 mg every 3 weeks for 15 cycles for about 1 year. On June 6, 2017, the abdominal MRI showed that most of the lesions in the margin, and all the lesions in the hilar and retroperitoneal lymph nodes had disappeared. It was speculated that the residual lesions at the margin might represent a surgical reaction. The patient was deemed to show a CR on September 14, 2017 and was still in remission at the last follow-up of January 10, 2019 based on PET-CT analysis. No side effects of pembrolizumab were observed. |
pmc-6505215-2 | Patient 2 (Fig. and Table ) is a 67-year-old male with no hepatitis virus infection. He underwent extended right hemihepatectomy, left hepaticojejunostomy, perihepatic lymphadenectomy, and portal vein reconstruction on May 16, 2017. The tumour measured 7.6 cm × 7 cm × 7 cm, with nerve invasion accompanied by microvascular invasion. No tumour was found in the liver margin and bile duct margin after the surgery. Lymphatic metastasis was detected in groups 8 and 12A. IHC showed Arg-1 (−), CK18 (+), GPC-3 (−), hepatocyte (−), Ki-67 positivity of 65%, and CK19 (+). Accordingly, he was diagnosed with iCCA stage IIIb. Similar to Patient 1, PD-L1 expression was detected on < 5% of the tumour cells, and the percentage of CD8+ T cells was 10%.
Lymph node metastasis in the hepatoportal area was detected using MRI and PET-CT on August 16, 2017. WES revealed 163 NSMs, including clinically actionable alterations in PTEN and TP53. In addition, TP53, SMAD4, and ARID2 are included in the COSMIC top 20 mutated genes (Additional file ). The TMB was 7.09 mutations/Mb, including 109 indels (66.87%) and 54 SNVs. The tumour exhibited pMMR and MSI (0.01%). He was started on a regimen of tegafur and pembrolizumab in late August. Unfortunately, he experienced the common adverse event to tegafur of pruritus, determined to be of grade 2 according to the standard CTCAE5.0 criteria. After withdrawing tegafur, the pruritus disappeared, and the drug was thus switched to an irregular administration schedule as of December 23, 2017 with an increase in the dose from 40 mg to 60 mg and to be taken twice a day until the beginning of February 2018. Pembrolizumab was administrated intravenously (150 mg every 3 weeks for six cycles). PET-CT scans revealed that the enlarged lymph nodes had disappeared. This CR was achieved in less than 4 months, and the patient continued to be in remission for 13 months up to the last follow-up. |
pmc-6505228-1 | The patient is a 63-year-old male who recently emigrated from Nigeria. He had
shortness of breath and acute progression of a chronic breast mass. The patient
reported having a right chest wall/breast mass since childhood but noticed
significant worsening for several months prior to being seen (). The mass had become enlarged,
firm and tender to the touch, and was associated with overlying skin changes. The
patient had also noticed a new mass in the ipsilateral axilla as well as an
unintentional weight loss of 15 pounds over the past year. Further history was also
notable for urinary retention and frequency for the past few months.
The physical examination revealed a remarkable large 4-cm firm, fixed right breast
mass with skin thickening and retraction. The patient also had firm right axillary
lymphadenopathy, diminished right-sided breath sounds throughout the entire right
lung field, and prominence of the left breast.
An admission chest X-ray was notable for complete opacification of the right lung
compatible with a large pleural effusion (). Further workup with computed
tomography scan of the chest revealed a 6 to 7 cm mass in the right breast with
right axillary adenopathy, a large right pleural effusion, and a 7-mm soft tissue
nodule at the left lung base (). Mammography could not assess the right breast due to the
inability to obtain adequate compression. However, it revealed marked gynecomastia
of the left breast. The patient underwent a diagnostic and therapeutic
thoracentesis, with pleural fluid studies consistent with an exudative effusion.
Cytology revealed metastatic adenocarcinoma of breast primary. The patient underwent
an ultrasound-guided core biopsy of the right breast mass with pathology revealing
invasive ductal carcinoma, grade 2, and positive for estrogen receptor (ER) 90%,
progesterone receptor (PR) 1% to 5%, and human epidermal growth factor receptor 2
positive, equivocal by immunohistochemistry, and positive by FISH (fluorescence in
situ hybridization; ).
For the urinary retention and frequency, a prostate-specific antigen was obtained and
elevated to 122.8 ng/mL. A prostate biopsy was done and revealed prostatic
adenocarcinoma, Gleason grade 8(5+3).
Due to his symptomatic pleural effusion, the patient was started on treatment for his
triple-positive metastatic breast cancer with docetaxel, trastuzumab, and pertuzumab
every 3 weeks with a plan for 6 cycles in total. He was also started on hormonal
therapy with tamoxifen. With regard to his prostate cancer, the patient was treated
with androgen deprivation therapy with leuprolide every 6 months. |
pmc-6505229-1 | A 48-year-old male from Veteran shelter with a history of hypertension, alcohol
dependence, and alcohol withdrawal seizures presented to the emergency department
for worsening tremors and inability to walk well due to severe shakiness and
unsteady gait for 1 week. On admission, he reported feeling anxious, agitated, and
excessive sweating but denied nausea, vomiting, headache, auditory, visual, or
tactile hallucinations. Review of the system was otherwise negative. He was not
taking any medication and denied smoking or using illicit drug use. He endorsed
drinking around 4 cans of 24 ounces of liquor daily and had been doing so for the
last 20 years, with his last drink being on the day of admission. He had multiple
detox admissions at our facility, with the last one being 6 months prior to the
admission. Physical examination revealed an anxious-looking white Hispanic male with
mild diaphoresis, tachycardia, tachypnea, and tremulousness. Computed tomography
scan of the head on admission did not reveal any intracranial pathology. We excluded
alcohol-related dementia and hepatic encephalopathy, based on his mentation,
Mini-Mental State Examination, mild ammonia elevation, ultrasonographic evidence of
mild hepatic steatosis without any increased nodularity of the liver, and a viral
serology that was negative for hepatitis panel including hepatitis A, hepatitis B,
and hepatitis C. The patient got admitted to step-down unit and intensive care unit
(ICU) for severe alcohol withdrawal and was managed with lorazepam tapering as per
hospital protocol. Along with fluid resuscitation, thiamine and folic acid were
supplemented. The first 2 days of the hospital stay were unremarkable; however, on
the third day, his condition deteriorated. He gradually started to get confused, and
by night, he was agitated and grossly disoriented while he was being treated with
scheduled intravenous (IV) lorazepam at a dose 2 mg every 6 hours along with
as-needed doses. Clinical deterioration warranted upgraded to ICU for DTs for close
monitoring on the same day. Despite the ICU standards of care, the patient
clinically worsened with marked confusion, complete disorientation, agitation,
aggressive behavior, and intense tactile hallucinations—the hallmarks of DTs despite
being on escalating doses of IV lorazepam. Regular laboratory draws did not reveal
any metabolic abnormalities. Neurology team was on board who suggested the
possibility of Wernicke’s encephalopathy despite the patient being on IV thiamine.
Other differentials included alcohol-induced dementia/amnestic syndrome; however,
our treatment continued along the lines of alcohol withdrawal. With every passing
day, the dose of benzodiazepines escalated, and lorazepam was subsequently replaced
with continuous IV infusion of midazolam on the 9th day. He showed some improvement
over the next 5 days and midazolam infusion was transitioned to lorazepam every 2
hours. However, on the 16th day of admission, he once again started manifesting the
classic sign of DTs. Lorazepam dosing escalated again, and on the same day, he had
to be restarted on midazolam infusion as he was not improving despite being on 2 mg
of lorazepam every 15 minutes for an hour. The neurology team suggested other
possibilities as the source of his confusion. There were no signs of infection or
any other cause of worsening delirium. Strong history of drinking and classic
presentation of DTs in the absence of any obvious metabolic, organic, or infective
causes with normal complete blood count, complete metabolic panel, computed axial
tomography scan of the head (), and a negative lumbar puncture/cerebrospinal fluid analysis.
We reconsidered to continue the treatment of DTs and restarted him on midazolam IV
infusion, which plateaued his symptoms, but he worsened with multiple attempts to
taper midazolam. Given the circumstances, on the 24th day of his admission, we added
phenobarbitone to the mix, starting at 60 mg every 8 hours while continuing
midazolam infusion. Within 2 days of starting this new combination, we were able to
taper off both the medications, and he was effectively transitioned to intermittent
lorazepam infusion. Any attempts to escalate tapering were met with new symptoms of
severe alcohol withdrawal. We subsequently were able to discontinue lorazepam
following 28 days of minimal tapering. Significant improvement of his symptoms with
eventual discharge to an inpatient drug rehabilitation program. He completed his
inpatient drug rehabilitation of 28 days and was devoid of any alcohol withdrawal
symptoms throughout his stay, before relapsing back to drinking again following
discharge. |
pmc-6505230-1 | We report a case of a 23-year-old female with a history of unrepaired ventricular septal defect (VSD) and pulmonary arterial hypertension with ES presenting with chest pain and shortness of breath. She was diagnosed with a membranous VSD at the age of 3 years and was noted to have pulmonary hypertension at the age of 8 years. She had self-discontinued all medications at 18 years of age. She had no history of prior thrombotic events and was not taking oral contraceptives.
Patient presented with sudden-onset, left-sided, pleuritic chest pressure radiating to the back with shortness of breath at rest. She had baseline 1 pillow orthopnea, but denied lower extremity edema and paroxysmal nocturnal dyspnea. On admission, she was found to be in moderate respiratory distress on high-flow nasal cannula with a 2/6 holosystolic murmur on cardiac auscultation. Blood pressure was 93/54 mm Hg, heart rate was 105 beats/min, and oxygen saturation was 96% on 70% high-flow oxygen. Laboratory findings revealed an elevated troponin greater than 50 ng/mL, brain natriuretic peptide of 7,575 pg/mL, and hematocrit of 38.6%. Electrocardiography on admission demonstrated new anterior Q waves and anterolateral ST elevations (). Bedside echocardiography revealed moderate hypokinesis of the basal to mid anterolateral wall. Patient was admitted to the medical intensive care unit.
Coronary angiography revealed a large organized thrombus in the mid-left anterior descending artery near the junction of a large septal perforator (). Patient underwent manual aspiration and thrombectomy with balloon angioplasty. There was distal embolization of thrombus in both the left anterior descending and a large septal perforator, seen on later angiography images (). There was no apparent atherosclerotic coronary artery disease. Right heart catheterization revealed central venous pressure 14 mm Hg, pulmonary artery pressure 105/58 mm Hg (mean pulmonary arterial pressure 72 mm Hg), and pulmonary capillary wedge pressure 35 mm Hg. Computed tomography pulmonary angiography demonstrated a dilated main pulmonary artery of 4 cm with no evidence of pulmonary embolism. Ultrasound Doppler of the extremities showed no evidence of deep vein thrombosis. Post-intervention echocardiography revealed an ejection fraction of 45%. Patient was placed on intravenous eptifibatide and continuous heparin infusion.
During intensive care unit course, the patient developed worsening respiratory compromise with desaturations on high-flow nasal cannula and bilevel positive airway pressure. Chest X-ray revealed new bilateral consolidations with concern for hospital-acquired pneumonia and impending acute respiratory distress syndrome. Patient was initiated on inhaled nitrous oxide, intravenous epoprostenol, and continued on macitentan and sildenafil. She required vasopressor therapy for hemodynamic support. Despite up-titration of pulmonary vasodilatory medications, she remained hypoxemic on bilevel positive airway pressure. She was intubated and emergently placed on VV ECMO support at a flow rate of 7 L/min. Hemodynamic parameters and oxygenation improved. Nitrous oxide was successfully weaned with down-titration of vasopressor therapy. Patient was accepted and transferred via emergent air transport to an outside hospital where she underwent successful heart-lung transplantation. Patient was seen in outpatient follow-up clinic at our institution and was ambulatory, independently living, and feeling well. |
pmc-6505231-1 | A 46-year-old female with a medical history of systemic sclerosis that has features of dermatomyositis presented to the emergency department (ED) with complaints of right-sided chest pain. She recalled having similar pain in the past, which was attributed to scleroderma flare-ups. Physical examination demonstrated multiple cushingoid features secondary to her chronic steroid use, along with digit contractures and shiny, tight-appearing digits. On admission, her electrocardiogram and chest X-ray were unremarkable; however, the patient progressively decompensated and developed intractable nausea and vomiting. The patient subsequently went into acute respiratory failure with an arterial blood gas demonstrating a partial pressure of oxygen (PaO2) of 69 on 15 L of oxygen, resulting in intubation. Repeat chest X-ray and computed tomography showed diffuse bilateral alveolar infiltrates as well as bilateral pleural effusions ( and ). Video bronchoscopy with bronchoalveolar lavage (BAL) was performed that showed numerous red blood cells, neutrophils, macrophages, and respiratory epithelial cells consistent with acute DAH, but was negative for hemosiderin-laden macrophages.
After a Rheumatology consultation, the patient was started on intravenous (IV) pulse–dosing Solu-Medrol 1 g daily for 5 days, her azathioprine was increased to 75 mg, and her hydroxychloroquine was discontinued. Plasmapheresis was not deemed necessary at this time. Two days later, a repeat chest X-ray revealed partial clearing of the previous extensive bilateral alveolar densities. On improvement of symptoms, the patient was successfully extubated and later discharged. Her rheumatologist was contacted to ensure follow-ups for further management and starting the patient on IV immunoglobulin (IVIG) as outpatient.
One month after discharge, the patient presented to the ED again, complaining of intractable nausea and vomiting. It was discovered that she had failed to start the outpatient IVIG therapy. During this admission, similar to the previous admission, the patient went into acute respiratory distress with a PaO2 of 59 on an arterial blood gas while on a 10-L non-rebreather mask. The chest X-ray at this time revealed interval development of alveolar infiltrates in the right lung (). A bronchoscopy with BAL again showed numerous red blood cells and neutrophils along with staining positive for hemosiderin-laden macrophages, thus confirming her second episode of DAH. She was started on IVIG inpatient for her scleroderma crisis, which had to be discontinued after she developed tonic-clonic seizures shortly after the treatment. After stabilization, the patient was discharged with a follow-up with rheumatology for further management of her systemic sclerosis.
Since this last discharge, the patient has returned to the ED multiple times for cardiac and recurrent pyelonephritis episodes, but has not had a recurrent episode of DAH again. |
pmc-6505262-1 | A 63-year-old woman of short stature was first admitted to our hospital three days after onset of acute aphasia, headache and a moderate right-sided hemiparesis. Medical history included type 2 diabetes, arterial hypertension, and past smoking. The patient had no history of mental retardation or cognitive decline up to the time of her acute illness. Whereas childhood and early adulthood were reportedly normal, she had developed hearing loss and diabetes at the age of 45 years. She was also diagnosed with cardiomyopathy that was initially thought to be of hypertensive aetiology, and had a history of chronic obstructive pulmonary disease (COPD) and renal insufficiency. Of note, the patient had two miscarriages, and one newborn child died within the first hours after birth. There was no history of previous frequent headaches. Her medication included aspirin, lercanidipine, candesartan, atorvastatin, fluticasone, salmeterol and insulin.
On admission, she presented with moderate fluent aphasia and moderate weakness of the right arm and leg. Laboratory testing revealed severe hypovolemic hyponatremia (116 mmol/l) and hyperglycaemia (19 mmol/l). Plasma osmolality was low (284 mmol/kg), whereas urine osmolality (457 mmol/kg), and urine sodium concentration were high (91 mmol/l). In addition, serum lactate (2.7 mmol/l), and serum creatine kinase (576 IU/l) levels were elevated. Computed tomography (CT) on admission showed hypodense areas within the left temporal lobe without signs of haemorrhage. CT angiography showed few calcified plaques in both carotid bifurcations without a relevant stenosis or occlusion of intracranial or extracranial arteries (Fig. ). Emboli detection on transcranial doppler was not performed. Magnetic resonance imaging (MRI) revealed fluid attenuated inversion recovery (FLAIR) hyperintensities within the cortical grey and white matter of the left temporal lobe (Fig. ). The patient was diagnosed with ischaemic stroke in the territory of her left middle cerebral artery and transferred to the stroke unit. Duplex sonography confirmed moderate atheroma of the right and left carotid bifurcation without relevant stenosis, which was considered a possible cause. Transthoracic echocardiography revealed left ventricular hypertrophy, but no cardiac sources of embolism. Electrocardiogram (ECG) monitoring showed no atrial fibrillation. Glycated haemoglobin was elevated (8.7%). LDL cholesterol was normal (1.15 mmol/l). Antiplatelet therapy was switched from aspirin to clopidogrel, and the patient was discharged after two weeks to a neurorehabilitation hospital with persisting moderate fluent aphasia.
Two weeks later, the patient was readmitted due to recurrence of the right-sided hemiparesis which now also involved her face. MRI revealed enlarging FLAIR hyperintense signal changes in the mesiotemporal area extending towards the left parietal lobe and left insula. In addition, new FLAIR hyperintense signal changes were also present in the right temporal pole (Fig. ). CT angiography again showed no vessel occlusion. The patient was diagnosed with a recurrent stroke. Holter-ECG over 4 days did not reveal any atrial fibrillation. Transoesophageal echocardiography did not reveal any patent foramen ovale or other cardiac source of embolism, but 4 mm thick plaques in the aorta were visible which were considered an additional possible cause for recurrent strokes. Clopidogrel was stopped and oral anticoagulation with a vitamin K antagonist (Phenprocoumon) was started.
During the second hospitalization impaired consciousness, recurrent vomiting and disorientation occurred. Electroencephalography (EEG) showed generalized slowing, and frequent multifocal rhythmic epileptiform discharges as well as sharp slow waves as signs of epileptic activity. Clinical course and EEG findings improved under antiepileptic therapy with lacosamide and levetiracetam. Cerebrospinal fluid (CSF) examination revealed normal cell count, normal protein, negative herpes simplex polymerase chain reaction (PCR) and elevated lactate levels. Laboratory screening for vasculitis turned out negative. Considering the longstanding nicotine abuse and hyponatremia, paraneoplastic encephalitis was also considered. However, CT thorax was normal and paraneoplastic antineuronal antibodies in serum (Anti-Hu, Anti-Yo, Anti-Ri, Anti-CV2, Anti-Ma1, Anti-Ma2/Ta, Anti-Amphiphysin, Anti-VGCC, and Anti-NMDA-receptor antibodies) turned out negative.
The patient was again discharged with residual aphasia and was able to return home where she was cared for by her husband. Six months later, the patient presented at the emergency department with disorientation, aggression, mutism and refusal to eat, drink or take her medication. She was diagnosed with organic psychosis and admitted to a psychiatric hospital. The patient was finally readmitted again nine months after initial hospitalization with repeated falls and progressive apathy. On admission, the patient was mutistic.
At this point, MRI showed progressive brain lesions involving both temporal and occipital lobes, characterized by a FLAIR-hyperintense oedema with signs of a local mass effect (Fig. ). Of note, these lesions crossed the boundaries of vascular territories. The parts of the lesions involving the cortex appeared hyperintense on diffusion-weighted imaging (DWI) and hypointense on apparent diffusion coefficient (ADC) maps, consistent with cytotoxic oedema. In contrast, subcortical regions appeared hyperintense on ADC maps, consistent with vasogenic oedema.
Taking into account the clinical presentation with recurrent stroke-like episodes, encephalopathy, seizures, headache and lactic acidosis, as well as the medical history including hearing loss, short stature, cardiomyopathy and diabetes, we suspected MELAS as the underlying cause. A detailed family history revealed hearing loss in a brother, and transient visual disturbances as well as a history of acute hearing loss in a sister (Fig. ).
A biopsy of the vastus lateralis muscle showed signs of mitochondrial myopathy, including sub-sarcolemmal accumulation of mitochondria on Gomori trichrome staining (so-called “ragged red fibers”), neutral fat deposits and prominent cytochrome C oxidase (COX) negative and succinate dehydrogenase (SDH) hyperreactive muscle fibres (Fig. ). Finally, the diagnosis of MELAS was confirmed by positive genetic testing for the m.3243A > G mitochondrial DNA mutation in the MT-TL1-gene - the most common mutation in patients with MELAS - in peripheral blood (7% heteroplasmy), as well as in the muscle biopsy (76% heteroplasmy).
The patient’s state worsened rapidly. The diagnosis and the lack of curative treatment options were discussed with her husband, who decided to care of the patient at home. The patient died shortly thereafter. |
pmc-6505284-1 | The index patient was a 3-year-old boy, and he was admitted to our hospital with repeated microscopic hematuria. Physical examination revealed no significant abnormality. The proband’s urine analysis just showed occult blood 2+ and no proteinuria. His serum creatinine level was 27 umol/L, and uric acid level was 175 umol/L. Serum IgG, IgA, IgM, C3 and C4 levels were normal, and ANA, dsDNA, and ANCA were negative. No cyst and high echogenicity were found in renal ultrasonography. Renal biopsy showed 4/35 glomerular segmental sclerosis, immunofluorescence were negative, renal interstitial fibrosis and renal tubular atrophy (Fig. ). His father was found with end-stage renal disease (ESRD) (Scr 1400umol/L) at the age of 29, and hematuria, proteinuria, edema and hyperuricemia (UA 776umol/L). Renal ultrasound showed several cysts in both kidneys (Fig. ). Other family members have no clinical manifestation of gout, CKD. There is a novel missense mutation(c.1648G > A,p.V550I) in exon 8 of UMOD gene, resulting in the conversion of valine to isoleucine. This mutation is extremely rare in the population, merely 0.0003 in the dbSNP database and 0.0009 in the Hapmap database for Asians. At present, there is no literature report on the pathogenicity of c.1648G > A mutation in the UMOD gene. This resulted in amino acid change that may affect the normal function of the protein. Sanger sequencing showed that the father and the pediatric patient carried the same mutation (Fig. ), in addition, the father’s clinical phenotype was consistent with ADTKD-UMOD. SCBC Genome Browser alignment results indicated that V550 in UMOD gene was highly conserved among different species (Fig. ) and its mutation to isoleucine is predicted to be harmful by Software analysis. |
pmc-6505292-1 | A 32-year-old G3P3002 African woman came from Yifag Kebele, Amhara Region, to Felege Hiwot referral hospital in Bahir Dar, Northwest Ethiopia in July 2016. She presented with abdominal pain and intractable vomiting of 1 day’s duration. She was also unable to pass feces and flatus and had developed progressive abdominal distension. She had a past medical history notable only for chronic gastritis for which she took unspecified medications and a past surgical history notable for a Cesarean hysterectomy after an intrauterine fetal demise during labor. As she had been told that her uterus was removed, she did not use contraception and had no menses. She was admitted to our surgical ward with a diagnosis of small bowel obstruction due to presumed post-operation adhesions and possible incisional hernia. She also had severe anemia and was resuscitated with 2 liters of normal saline and transfused with 2 units of blood. A plan was made to correct the hernia once she was stabilized. After 2 days in our hospital, however, her condition worsened and a consultation was made to Obstetrics and Gynecology for further evaluation.
On physical examination at the time of consultation, she was confused and irritable, with an undetectable blood pressure and a thready pulse of 132. She had labored breathing, pale conjunctiva, and a distended abdomen with a palpable mass below the midline surgical scar. An abdominal examination also revealed a fluid wave and hypoactive bowel sounds. Laboratory testing showed a white blood cell count of 12.9 × 103 with 88.4% neutrophils and hemoglobin of 5.8 g/dl. Urine human chorionic gonadotropin (hCG) was positive. A transabdominal ultrasound showed a normal liver, spleen, pancreas, and kidneys. There was a significant debris-filled intraperitoneal fluid collection, especially on the right side of her abdomen, with a deepest pocket measuring 5 cm. No lymphadenopathy was seen. A singleton, viable pregnancy was identified measuring 13 weeks of gestational age with no gross abnormality and adequate amniotic fluid.
The Obstetrics and Gynecology team diagnosed hypovolemic shock secondary to ruptured ectopic pregnancy, and our patient was taken to the operating room for a laparotomy. Intraoperative findings included 4.5 liters of hemoperitoneum, a cervical stump pregnancy with well-formed fetus and intact gestational sac, and active bleeding from partially detached placental site. While the left ovary appeared normal, the right ovary and both fallopian tubes were absent.
The ectopic gestation was clamped at its base and resected from the cervical stump. Bleeding sites were ligated to ensure hemostasis. Our patient was deemed too unstable for trachelectomy. Her abdomen was irrigated with warm saline and the incision closed in layers. She was transferred to our intensive care unit (ICU) for aggressive volume resuscitation with 8 liters of normal saline and 5 units of blood, and a dopamine drip was initiated to assist with blood pressure control. After 2 hours, her blood pressure had stabilized and she was discharged 9 days later. On follow-up at fourth week post-operation, she was healing well and had hemoglobin of 11 g/dl. |
pmc-6505311-1 | A 31-year-old, otherwise healthy man presented to our clinic with a 7-day history of central scotoma and metamorphopsia in his right eye. A local dermatologist had diagnosed an erythema involving maculopapular and vesicular eruptions on both hands, feet, and inside his mouth as HFMD 2 days before his visual symptoms began (Fig. a and b). A few days before the erythema’s onset, the patient had complained about severe fatigue, sore throat, fever, and chills. Two weeks before symptoms’ onset, his 4-year-old daughter presented similar symtoms and signs of HFMD.
At his initial ophthalmologic examination, best corrected Snellen visual acuity was 20/400 in the right and 20/20 in the left eye. Intraocular pressure was 15 mmHg in both eyes. Goldmann peripheral visual field testing was within normal limits in the left eye (Fig. a) and revealed a central scotoma in the right eye (Fig. b). Slit lamp examination showed no cellular infiltration in the anterior chamber in either eye. Fundus examination of the right eye revealed central and parafoveal retinal pigment epithelium (RPE) irregularities and yellow retinal dots (Fig. B1). Fundus autofluorescence (FAF) demonstrated focal dots of decreased FAF surrounded by increased FAF corresponding to funduscopically detected focal alterations in the retinal RPE, and yellow retinal dots (Fig. B2). The left eye revealed no abnormalities. Spectral domain optical coherence tomography (SD-OCT) demonstrated irregularities in the ellipsoide zone, as well as hyperreflective dots in the RPE (Fig. B3). Fundus fluorescein angiography (FAG) exhibited central hypofluorescence in the macular area in the early phase, and focal hyperfluorescence in the late phase corresponding to RPE defects observed in FAF (Fig. B1). No macular exudation, extramacuar abnormalities or signs of vasculitis were observed. Indocyanine green angiography (ICGA) showed central hypofluorescence in the early and late phase (Fig. B2).
One month after initial ophthalmologic examination, visual acuity of the right eye improved spontaneously and reached 20/25 (left eye 20/20). Dermatological lesions subsided and only fingernail onychomadesis persisted. SD-OCT revealed persistent RPE changes (Fig. C3). The focal areas of increased autofluorescence changed to areas of decreased autofluorescence (Fig. C2) - changes that were associated with a subjectively improved vision and alleviated scotoma.
Three months after his initial ophthalmologic examination, the patient was symptom-free. Interestingly, SD-OCT now revealed subretinal fluid, which increased until 6 months after the initial examination (Fig. D3). FAG und ICGA showed no signs of choroidal neovascularization (Fig. C1 + 2). Since the patient was symptom-free, no systemic or local therapy was prescribed. A year after his initial examination, the right eye’s visual acuity was stable at 20/20, there was no detectable scotoma (Fig. c), and the subretinal fluid had resolved spontaneously (Fig. E3) while FAF exhibited persistent areas of hypoautofluorescence (Fig. E2).
In addition to the conventional examinations, we conducted OCT-A (Zeiss Cirrus 5000 AngioPlex®) at his initial examination and at all follow-ups. Corresponding with the area of focal dots of decreased FAF surrounded by increased FAF and central hypofluorescence in the FAG and the ICGA, the choriocapillaris (CC), detected by OCT-A, revealed reduced flow at initial examination (Fig. B5). Over time, CC architecture recovered nearly completely (Fig. C2-E2), whereas anomalies in FAF, FAG and ICGA also changed, but remain. |
pmc-6505638-1 | 71-year-old female with a history of renal failure on dialysis who presented for transcatheter aortic valve replacement (TAVR) evaluation. Part of the routine preprocedural TAVR workup includes assessing the abdominal aortic vasculature for extent of atherosclerotic disease. The patient’s body mass index was 28. As per the department low contrast dose protocol, the patient was injected with 25 mL Isovue 370 at a rate of 4 mL/sec followed by a 40 mL saline chase. Bolus tracking technology was used to trigger the scan once enhancement reaches 10 Hounsfield Units (HU) over baseline. Images in Fig. are reconstructed in both conventional and virtual monoenergetic images at 40 keV.
The abdominal aorta vascular anatomy was targeted for segmentation. Despite the low volume contrast bolus, the low 40 keV VMI data demonstrated a greater than two-fold increase in HU of the abdominal vessels compared to conventional CT. A combination of thresholding and iodine mapping segmentation tools were utilized. These tools generated a more accurate 3D volume rendered model of the abdominal vasculature lumen using the 40 keV VMI data compared to conventional CT with minimal manual segmentation required. The final 3D printed model of the abdominal vasculature lumen using the VMI at 40 keV was designed and completed for vascular access simulation (Fig. ). |
pmc-6505638-2 | 77-year-old male with a history of atrial fibrillation who presented for preprocedural planning for left atrial appendage closure device. Part of the preprocedural workup includes helical cardiac CT with retrospective gating. The scan delay is a threshold/trigger-based hybrid with the scanner manually started once the user sees the first blush of contrast in the right atrium. The patient received 25 mL of iodinated contrast Isovue 370 at 4 mL/sec followed by a saline bolus.
Conventional arterial phase images (not shown) demonstrate a filling defect in the anterior aspect of the left atrial appendage (LAA), which may be related to thrombus or circulatory stasis. To confirm and better delineate the thrombus, a 30 s delayed conventional CT scan (Fig. a) is obtained, which poorly demonstrates a persistent LAA filling defect, consistent with thrombus.
A 3D printed model was requested for patient education. However, the scan had a very washed out appearance and segmentation of the thrombus using conventional CT data only did not yield an accurate model due to limited attenuation differentiation. The corresponding 40 keV VMI from the delayed phase (Fig. b) elegantly demonstrates a thrombus in the left atrial appendage. There was a two-fold increase in HU values between the conventional and VMI target anatomy. Using the 40 keV VMI data set, the thrombus volume was well defined, and the resulting 3D printed model was anatomically 1:1 scale (Fig. d). |
pmc-6505638-3 | 64-year-old male with a history of stage IIA (T1bN1M0) squamous cell carcinoma of the lung status post right pneumonectomy and chemotherapy who was found to have a focal upper right tracheal abnormality on his two year follow up routine CT Chest with contrast (90 mL intravenous Optiray 350) (Fig. a). Originally, this was suspected to be adherent mucous within the trachea. However, closer analysis using the VMI data reconstructions revealed enhancement and iodine accumulation, which was highly suspicious for neoplasm recurrence (Fig. b). He subsequently underwent bronchoscopy and pathology revealed squamous cell carcinoma suspected to be local regional recurrence versus a new primary malignancy.
A 3D model was requested for operative planning and resident physician education. Segmentation of the airway with the proximal tracheal lesion was technically feasible on both conventional and VMI data. However, there was a subjective decrease in segmentation time when using VMI. Additionally, there was a subjective increase in confidence when selecting the appropriate margins of the tracheal lesion with respect to the surrounding anatomy due to the significant increase in HU differentiation between conventional and VMI. |
pmc-6505638-4 | 45-year-old-male with history of trauma to the left upper extremity after involvement in a motor vehicle accident. The patient underwent open reduction internal fixation of the left proximal surgical neck and distal humeral shaft fractures with intramedullary rod nailing. After returning ten weeks post-operatively, the patient’s range of motion had improved. However, there was residual left shoulder pain and migration of the proximal hardware screw. A SDCT without contrast of the left upper extremity was performed and demonstrated improved fracture visualization but minimal bony bridging or callus formation.
Attempts at segmentation using the conventional CT alone were limited due to the extensive beam hardening artifact originating from the metallic intramedullary orthopedic hardware (Fig. a). Using the high 120 keV VMI data, the metal artifact was significantly reduced enabling the auto-segmentation tools to easily differentiate the osseous fracture fragment margins (Fig. b). Hounsfield Unit values of the osseous structures adjacent to the metal hardware were reduced by 90% on high keV VMI compared to conventional CT. The resulting 3D printed model clearly demonstrated the fracture margins and outline of intramedullary orthopedic hardware.
For all four cases, the differential in calculated Hounsfield Units between conventional and VMI data at the region of interest (ROI) for segmentation is listed in Table . Comparative and differential calculations were also made between the segmented ROI HU and the adjacent tissue material HU. The average primary pre-processing and segmentation time for each of the cases was approximately 60 min. Additional STL mesh post-processing for each model required an additional 30–60 min. 3D printing time averaged between two to five hours each depending on the case, size, and scale of the models. |
pmc-6505722-1 | A 75-year-old male former smoker with 45-pack year history of tobacco abuse initially presented with swelling of the left neck, followed by progressive hoarseness and dysphagia over a course of one to two months. A biopsy of the left neck node demonstrated squamous cell carcinoma (SCC), p16 positive. The patient also had a CT scan and follow-up positron emission tomography-CT (PET-CT) showing a 4.5 cm x 7 cm mass involving the left hypopharynx and oropharynx, crossing midline and causing narrowing of the hypopharyngeal and supraglottic airway. There was also bulky left level II neck lymphadenopathy measuring up to 7 cm in diameter. The patient was also found to have three fluorodeoxyglucose (FDG) avid lung nodules as well, one of which was subsequently biopsied, confirming metastatic p16 positive SCC. The patient required tracheostomy and gastrostomy placement for threatened airway obstruction and dysphagia, respectively. He was initially enrolled on a clinical trial comparing first-line EXTREME chemotherapy versus ipilimumab and nivolumab, and was randomized to combination ipilimumab and nivolumab delivered concurrently every three weeks for four cycles. Follow-up imaging at eight weeks showed progression of disease, with growth of the primary and neck masses ulcerating through his skin (Figure ), as well as disease progression in the chest, with growth of previous nodules and development of additional pulmonary nodules, the largest measuring 2.4 cm (previously 1.6 cm, Figure ).
The patient had worsening symptoms associated with mass effect in the neck and was re-evaluated by Radiation Oncology at the request of the treating oncologist. He was treated with ‘QUAD SHOT’ for palliation [], delivering 3.7 Gy BID x 2 days (total dose 14.8 Gy) to gross disease, and 3.3 Gy BID x 2 days (13.2 Gy) to microscopic areas at high risk for disease, including one nodal echelon beyond gross disease on the left (levels IB-V), and contralateral levels II-IV. No radiation was delivered to his lung disease. The patient continued through the third and fourth cycles of nivolumab and ipilimumab without breaks or delays. Radiation was delivered during the three-week time frame between immunotherapy cycles, and he tolerated treatment well with minimal pain and noticeable improvement in the left neck mass.
On follow-up CT scan at two weeks after completion of radiation, the primary and bulky left neck adenopathy had decreased in size by approximately 25% (Figure ). The metastatic pulmonary nodules had also all decreased in size with the largest nodule decreasing from 2.4 to 1.3 cm, approximately 50% (Figure ). His QUAD-SHOT regimen was repeated one month after initial treatment, as described above. Repeat imaging showed continued decrease in size of all neck and most lung disease, with one lung nodule minimally increasing in size. The patient received a third round of QUAD-SHOT as described above, with near complete resolution of his left neck mass. At 16 weeks from first round of radiation treatment, the patient had a continued response in his pulmonary metastases, followed by disease stability. At 20 weeks from start of radiation, one of his lung lesions had increased in size while the remaining lesions were either stable or decreased in size. At the time of this writing (10 months from initial diagnosis), he has completed a total of 14 cycles of ipilimumab and nivolumab on trial and is currently living with stable, asymptomatic disease. |
pmc-6505723-1 | A 70-year-old female presented to our office with localized left leg swelling of two days duration after taking diclofenac for hip pain. The patient had a past medical history of hypertension, diabetes mellitus, asthma, osteoarthritis, and iron-deficiency anemia. She denied a history of any underlying autoimmune disease or inflammatory bowel disease. Her left lower extremity was red and had a localized fluctuant swelling of 2 x 2 cm with surrounding cellulitis. This was thought to be an abscess; incision and drainage (I and D) were performed on this visit. The patient was given amoxicillin-clavulanate and doxycycline with follow-up in one week.
On the next appointment, the abscess had worsened despite the antibiotics. The abscess was again opened and drainage was collected for culture and gram stain. On this visit, the patient’s antibiotics were changed to trimethoprim-sulfamethoxazole for one week. Cultures from this I and D were negative for any organism and so was the gram stain.
On the third visit, one week later, the wound had enlarged and was open (Figure ). At this point, the patient was admitted to the hospital for further evaluation of a non-healing ulcer. On examination, the patient was afebrile and there was a 4.6-cm lesion on the pre-tibial area of the left lower extremity with undermined borders and denuded tissue and areas of necrosis as the base. Mild to moderate serous fluid drainage was seen with the surrounding area of erythema. Laboratory evaluation revealed the white blood cell count to be 9.28 x 103/mL. MRI of the affected leg was done and it showed no evidence of osteomyelitis (Figure ). Dermatology was consulted and punch biopsy was obtained. A sample of 0.3 x 0.3 cm was excised with a depth of 0.4 cm, and the sample was sent for microbiologic and pathologic analysis. On pathologic analysis of the sample (Figure ), it was reported as severe acute cellulitis, abscess formation and granulation tissue which could potentially represent PG if infectious etiology can be completely ruled out. Microbiological analysis was negative for acid-fast bacilli, gram stain, or periodic acid-Schiff stain.
On the basis of two negative cultures, failure to respond to antibiotics, and pathologic analysis, the diagnosis of PG was established. The patient was started on oral prednisone 100 mg and high-potency topical steroids. After a couple of days, there was a marked reduction in erythema and ulcer showed signs of healing. A workup for secondary causes including recent EGD and colonoscopy was negative for malignancy and inflammatory bowel disease, and there was no evidence of any inflammatory or rheumatologic condition. On follow-up at one week after hospital discharge, the wound was found to be improving. |
pmc-6505724-1 | A 19-year-old female, with a history of two pregnancies, neither of which reached a gestational age of 24 weeks, a current viable intrauterine pregnancy at 32 weeks and past medical history of recently diagnosed unspecified psychosis, methamphetamine use disorder and history of multiple incarcerations, was brought in by ambulance to our psychiatric emergency room from a women’s correctional facility. She presented with persistent delusions, paranoia and persecutory thought content related to her pregnancy.
During her psychiatric evaluation in the emergency department, the patient reported having auditory and visual hallucinations. She was observed responding to internal stimuli, displayed disorganized thought process, and was notably agitated, all in the context of primary psychosis versus drug-induced psychosis. She had been prescribed 300 mg of quetiapine daily before this hospitalization, but was unable to confirm or deny whether she had been taking the medication as prescribed.
At the start of this hospitalization, she was given quetiapine 300 mg twice daily for three days. She also received, as needed, a 3-mg intramuscular dose of haloperidol for acute agitation and violent behavior.
Her prescribed quetiapine dose was subsequently increased to 400 mg twice daily for another four days, but her ongoing aggression resulted in an additional intramuscular dose of 5 mg of haloperidol.
Because of poor response on this antipsychotic regimen, with continued auditory hallucinations and psychotic agitation, the patient was cross-titrated from quetiapine 400 mg twice daily to haloperidol 5 mg twice daily. During this time, she attempted to elope from the unit on three separate occasions due to persecutory delusions. She also continued to exhibit disorganized and aggressive behaviors towards staff, but no restraints were used. In addition, the patient began to develop sialorrhea and mild tremors. Due to the onset of these symptoms, haloperidol dosing was reduced to 5 mg once daily. The patient was also started on diphenhydramine 25 mg daily for her mild tremors, sialorrhea, and muscle rigidity, which were initially thought to be extrapyramidal symptoms caused by haloperidol. Labs were drawn and indicated a white blood cell count (WBC) on the upper limits of normal (10.8). Her basic metabolic panel (BMP) was notable for Na of 132, aspartate transaminase (AST) of 50, lactate dehydrogenase of 213 and creatine kinase of 1029. She was afebrile, but tachycardic with a pulse as high as 119.
The patient continued to be monitored, but remained aggressive and violent towards staff and received an additional 3 mg intramuscular dose of haloperidol. Her muscle rigidity persisted and she began complaining of worsening stiffness.
On hospital day 21, her care was transferred to the inpatient medicine team due to increased clinical suspicion for NMS. Her vitals remained stable. Labs were redrawn and showed an uptrending WBC of 11.5, partial thromboplastin time (PTT) of 440’s, D-dimer of 2640, Na of 133, alkaline phosphatase of 186, AST of 76, lactate dehydrogenase of 265 and uptrending creatine kinase at 2,320. She was given supportive care with 100 cc/hr intravenous normal saline maintenance and was monitored for autonomic instability including tachycardia, arrhythmia, and blood pressure lability, which are known to characterize NMS [].
Her labs were then redrawn after normal saline infusion and indicated uptrending creatine kinase to 2,405, lactate dehydrogenase to 272, AST to 79 and alkaline phosphatase to 189 along with tachycardia and otherwise stable vitals.
Five days after being transferred to inpatient medicine, she was admitted back to the psych inpatient unit with stable vitals and a down trending creatine kinase (CK) at 940. Her muscle rigidity, sialorrhea and tachycardia had also resolved. Upon transfer back to the inpatient psychiatric ward, all antipsychotics were stopped and she was started on 1 mg of lorazepam as needed for agitation.
At 39 weeks gestation she was transferred to the inpatient obstetrics unit for induction of labor. She was given 1 mg of lorazepam for agitation during delivery. She had a normal, spontaneous vaginal delivery of a baby boy without complications. Two days after delivery, her psychiatric hold allowing her to be detained in a hospital setting expired. She was discharged into a transitional care setting, with close outpatient follow-up. An antipsychotic regimen was not restarted at the time of discharge due to ongoing concerns that NMS had not resolved for at least two weeks prior to the rechallenge process. |
pmc-6505725-1 | The patient was a 37-year-old female who developed sudden breathy hoarseness and dysphagia two weeks after childbirth, with an associated headache that persisted for 14 days. An initial otolaryngologist evaluated the patient shortly after symptom onset and noted bilateral vocal fold paralysis on flexible laryngoscopy. Subsequent imaging included a computed tomography (CT) scan of the neck and chest as well as a magnetic resonance image (MRI) of the brain, both of which were unremarkable. A trial of antibiotics, which was attempted because of concern for pharyngitis, was ineffective. She was also offered steroids; however, she declined to take them for fear of breast milk transmission. She was then referred to a dedicated laryngologist as well as neurologist for further work up.
The patient was evaluated by another otolaryngologist, who, on flexible laryngoscopy, noted bilateral vocal fold paralysis with the vocal folds fixed in the intermediate position as well as a mild palatal weakness indicative of a high vagal injury. Videostroboscopy three months after symptoms showed continued bilateral vocal fold fixation in the intermediate position but some slight movement of the arytenoids towards midline with maximal effort. Laryngeal electromyogram performed four months after symptoms showed evidence of severe denervation of the left thyroarytenoid muscle, neurogenic injury of the right thyroarytenoid muscle with evidence of reinnervation, and mild injury of the left cricothyroid with normal signals from the right cricothyroid (Table ).
Repeat flexible laryngoscopy showed abduction and adduction of the right vocal fold but no movement on the left. Follow up exam six months after symptoms showed a normal function of the right vocal fold and near-normal function on the left. At this time, she noted that her voice was almost at baseline. At final follow-up nine months after symptoms, she had a complete return of bilateral vocal fold function and voice improvement back to her baseline. |
pmc-6505728-1 | A 77-year-old man with a past medical history of type 2 diabetes, hypertension, and ESRD underwent deceased donor renal transplantation. Two months following his renal transplant, the patient was admitted for an acute kidney injury discovered on routine follow-up laboratory testing. From a baseline creatinine of 1.3 mg/dl after the transplant, he was noted to have a creatinine of 2.7 mg/dl and a renal biopsy was obtained. Histopathology was suggestive of mildly active cellular rejection and acute tubular injury but with no concerns for antibody-mediated rejection. The patient received three days of methyl-prednisolone 250 mg daily intravenously and was subsequently transitioned to high-dose oral prednisone with a taper.
The patient was readmitted within three weeks of his renal biopsy with worsening renal functions, now with a creatinine level of 3.8 mg/dl. At this time, he was on prednisone five mg daily, tacrolimus four mg twice daily, and mycophenolate 500 mg twice daily. His family reported poor oral intake and that he had been taking furosemide at home. He received intravenous (IV) normal saline and diuretics were held. However, as his renal functions did not improve beyond a creatinine level of 2.1 mg/dl, the decision was made to perform a repeat renal biopsy. During ultrasonography for the renal biopsy, concerns were raised for a possible renal artery aneurysm. An ultrasound of the right lower quadrant and transplant kidney subsequently showed a 3 cm x 3.4 cm x 4 cm aneurysm proximal to the renal artery anastomosis to the right external iliac artery (Figure ). The right external iliac artery to renal artery anastomosis was patent and the renal vein was noted to be patent as well. No peri-transplant kidney fluid collections were noted and no hydronephrosis was seen.
Subsequently, a pelvic arteriogram was performed, which showed patent pelvic and iliac arterial flow. However, a large pseudoaneurysm arising directly off the right external iliac artery was re-noted and the renal transplant artery was noted to be filling from the distal side of the aneurysm and remained patent, although with sluggish flow (Figure ). A second known renal transplant artery was not seen and was presumed to be thrombosed.
While the interventional radiologist considered closing off the pseudoaneurysm by stent placement, the origin of the aneurysm was noted to be too close to the anastomosis to allow for stent placement. Hence, transplant surgery was consulted. The patient was taken to the operation room for a re-exploration of his transplanted kidney and revision of the arterial anastomosis. The patient underwent exploratory laparotomy, and intraoperatively, significant inflammation and scar tissue surrounding the hilum of the transplanted kidney was seen. Once the pseudoaneurysm was entered, necrotic tissue and purulence within the pseudoaneurysm were noted. It was felt that the arterial flow to the transplanted kidney could not be restored and, therefore, a decision was made to proceed with the resection of the infected pseudoaneurysm and transplant nephrectomy. The transplanted kidney was explanted. A portion of the pseudoaneurysm was sent to pathology for further characterization, and a portion was sent to microbiology for culture. The explanted kidney was also sent to pathology for further analysis. The patient was transferred to the intensive care unit (ICU) postoperatively for further management and close monitoring. During the surgery, the patient received crystalloids and multiple blood products.
On arrival to the ICU, the patient had temporary dialysis access placed and started on continuous renal replacement therapy (CRRT). Given concerns for an infected pseudoaneurysm, he was empirically started on renally dosed vancomycin, piperacillin-tazobactam, and fluconazole. All immunosuppressive agents were discontinued at this time. Due to persistent vasopressor requirements while in the ICU, the patient was switched to vancomycin, meropenem, and micafungin. The infectious disease team was consulted for recommendations. Blood bacterial and fungal cultures remained negative. However, fungal cultures from the pseudoaneurysm grew Aspergillus flavus on three separate samples. The patient was then transitioned to IV isavuconazonium 372 mg every eight hours for six doses, followed by 372 mg daily with a plan to continue for at least six weeks. Vancomycin and meropenem were discontinued. The pathology of the explanted kidney showed transmural necrosis of the renal artery, no evidence of rejection, and scattered micro-abscesses within the parenchyma. As the patient improved clinically, he was transitioned from CRRT to intermittent hemodialysis. He was subsequently transferred out of the ICU in stable condition. His hospitalization was complicated by colitis secondary to Clostridium difficile for which oral vancomycin was initiated. Preparation was made to discharge him to an acute rehabilitation facility; however, a day prior to discharge, he was found to be unresponsive by his nurse and despite prolonged resuscitation attempts for cardiac arrest, could not be revived. The exact etiology for this sudden demise could not be determined. |
pmc-6505730-1 | A 61-year-old African-American man presented with two months history of severe post-prandial nausea, vomiting and bloating. He also reported generalized fatigue, anorexia and unintentional weight loss of 20 pounds. He remained an active smoker with a 20-pack-year smoking history but denied any alcohol consumption or illicit substance use. His medications included ondansetron and pantoprazole tablets with minimal symptom relief. On admission, vital signs were only significant for slight tachycardia of 94 beats per minute. General physical examination revealed cachexia, temporal muscle wasting and clubbing of nails in both hands. The remainder of his examination was unremarkable. At this point, our differential diagnoses for his symptoms included gastrointestinal (GI), endocrine, metabolic, and psychiatric causes. From a GI perspective, we considered gastroparesis, gastric outlet obstruction, GI malignancy and cyclical vomiting syndrome.
Investigations
The following investigations were normal or negative: blood urea nitrogen, serum creatinine, serum potassium, serum total calcium, bilirubin, alanine aminotransferase, aspartate aminotransferase, serum lipase, urinalysis, chest X-ray and electrocardiogram. In addition, the patient had a computed tomography (CT) scan of the abdomen and pelvis on admission demonstrating residual food and fluid in his stomach despite fasting concerning for delayed gastric emptying. An esophagogastroduodenoscopy (EGD) was performed early in the admission and was seen to be normal. Scintigraphic gastric emptying studies were performed and gastric emptying time was calculated from anterior images acquired for approximately 90 minutes. The percentage of residual tracer within the stomach at two hours was 75% consistent with delayed gastric emptying or gastroparesis. A small bowel follow was also consistent with generalized GI hypo-motility disorder of unclear etiology.
He was screened for potential underlying causes for his gastroparesis. His fasting plasma glucose and hemoglobin A1c levels were normal ruling out diabetes mellitus. Hypothyroidism and connective tissue disorders were also ruled out by normal thyroid stimulating hormone levels and negative autoimmune panel, respectively. His neurological examination was entirely normal and had no history of recent viral illness or prior gastric surgery. None of his medications were particularly associated with a delay in gastric emptying. In view of his significant weight loss and active smoking a CT scan of the chest was performed which revealed a spiculated nodule sized 9 mm in right upper lobe of the lung (Figure ) along with right hilar lymphadenopathy (Figure ). A positron emission tomography (PET) scan was performed with hyper-metabolic activity in the right upper lobe nodule (Figure ) and right hilar lymphadenopathy (Figure ). Nodule resection and biopsy revealed a poorly differentiated non-small cell lung carcinoma (Figure ) with no evidence of local or distal metastasis on PET scan and CT scan of the brain with intravenous contrast. Due to the concern for paraneoplastic origin of his gastroparesis further serological testing revealed positive anti-neuronal nuclear antibodies type 1 (Anti-Hu) and cytoplasmic purkinje cell antibodies (Anti-Yo).
Treatment and outcome
The patient was diagnosed with a paraneoplastic gastroparesis secondary to occult non-small cell lung cancer. He was started on a chemotherapy combination of Carboplatin and Paclitaxel with a three-week course of local radiation therapy. Moreover, for the relief of his severe GI symptoms dietary modifications, pro-kinetic agents and psychological counselling were used with gradual clinical improvement observed on follow-up visits. |
pmc-6505731-1 | A seven-year-old female with no significant past medical history initially presented with a syncopal episode while at a birthday party, with loss of consciousness for 2-3 seconds and mild upper body stiffness without a postictal state. The patient reportedly was on the swing at a local park when she experienced her syncopal episode. As per her mother, who watched the entire episode, she did not fall off the swing and immediately returned to normal activity. The patient had no prior history of syncope, headaches, seizures, vomiting, diplopia, or blurry vision, and no family history of seizure disorder, cardiac abnormality, CNS disorder, or AVM. Upon follow up with her pediatrician the next day, the patient was alert, happy, and in no apparent distress. A comprehensive physical exam performed including extensive neurological examination was unremarkable.
Despite this, the pediatrician chose to order a head CT to rule out intracranial pathology, as well as a CBC with differential, CMP, thyroid profile, 2D echo with doppler of the heart, and 12-lead electrocardiogram. All her laboratory results were within normal limits. Head CT revealed marked abnormality to the thalamus, lateral ventricle, and the periventricular area on the right side extending into the foramen of Monroe and causing hydrocephalus. Based upon this, a differential diagnosis including brain tumor, AVM, and neurofibromatosis was developed.
At this point, the pediatrician ordered an MRA that showed an AVM. The patient was subsequently sent for an MRI of the brain with gadolinium which revealed hydrocephalus and a large AVM involving mainly the thalamus on the right side and the basal ganglia with large intraventricular draining veins into the galenic venous system (Figure ). The size of the malformation was noted to be 5 cm x 4 cm x 3 cm. There were no signs of intracranial hemorrhage. Cerebral angiogram confirmed these findings (Figure ).
Three subsequent neurosurgical evaluations demonstrated an unremarkable neurological examination with no asymmetries on cranial nerve examination, strength, muscle tone, or reflexes. Her sensory and cerebellar examinations were within normal limits as well, and the neurologist concluded that the AVM was not associated with any neurological deficits and no symptoms referable to the ventricular obstruction. An EEG obtained showed no abnormalities. An ophthalmology consult demonstrated a normal ophthalmological examination with no evidence of AVM in the retina. Due to the AVM size and structural involvement, surgery was ruled out as a possible course of treatment. All neurosurgical consults concluded that the patient should receive routine imaging every six months to ensure no change in size and bleeding status. A repeat MR angiogram (Figure ) and MRI eight months after the original confirmed no increase in overall size of the vascular malformation. The patient was routinely monitored with follow up CT and MRI scans every six months for the next six years, which demonstrated no change in size of her AVM and no evidence of bleeding. The patient also exhibited no signs of neurological deficit, and never experienced a repeat syncopal episode during this time. She was then lost to follow up and passed away as a result of AVM rupture 12 years after presentation. |
pmc-6505735-1 | A 38-year-old, otherwise healthy, right-handed man presented with a two-year progressive history of motor dysphasia and a three-month history of progressive right-hand weakness. The patient also had one short episode of right leg numbness and weakness. A neurological examination showed reflex asymmetry (right > left), hemihypesthesia, hemiparesis (4/5), and positive Babinski sign on the right. Magnetic resonance imaging (MRI) of the brain revealed a 54 x 54 x 52 mm cystic lesion of the left frontal lobe in front of the precentral gyrus with a septum attached to the posterior wall of the cyst. The cyst was hypointense on T1-weighted images (T1WI) (Figure ) and hyperintense on T2-fluid-attenuated inversion recovery (FLAIR) scans (Figure ).
MRI scans with gadolinium showed a slight contrast accumulation in the cystic walls and homogeneous accumulation in the septum without perifocal edema (Figure ).
The medial part of the tumour was in close proximity with the left lateral ventricle and subarachnoid spaces were shallow on the left with a 7-mm midline shift present.
The patient was admitted for further examination and treatment. The differential diagnoses included astrocytoma, ganglioglioma, ependymoma, parasitic cyst, and supratentorial cystic hemangioma. The serological examination for echinococcus granulosus was negative and blood examination was normal. Although the final diagnosis was not established, the mass effect was causing clinical deterioration and the patient elected to proceed with surgery for removal of the cystic tumour. Following fronto-temporal craniotomy and a minimal corticotomy, the cystic cavity filled with yellowish fluid was entered. An intraoperative cystic wall biopsy revealed a normal brain tissue and the tumour was found forming the septum on the posterior wall (Figure ).
The tumour was dissected from the cyst and removed. Taking into account the proximity of the corticospinal tracts and pathology results, the cystic wall was left intact.
The patient had a non-complicated postoperative course with a full neurological recovery and was discharged on the seven postoperative day. The patient underwent a complete neurological and radiological re-examination eight months after the surgery. He was neurologically intact, MRI showed a residual 2-cm cyst with no enhancement with gadolinium contrast administration (Figures , ).
He remained symptom-free three years after surgery with a further decrease in the size of the residual cyst on MRI (Figures , ).
Pathology
The intraoperative specimen of the cyst wall was frozen at -15 degrees of Celsius and normal brain tissue was identified on the frozen section slide (Figure ).
The tumour specimens were fixed in 10% neutral-buffered formalin, processed, and embedded in paraffin, then 3-μm-thick paraffin sections were stained haematoxylin and eosin (H&E) and 5-μm sections were stained immunohistochemically for glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67 protein. Histologically, the tumour consisted of morphologically and immunohistochemically distinct components. Small pseudopapillary structures were seen consisting of hyalinized small vessels (Figure ), which were covered by GFAP-positive pseudo stratified glial cells with small round nuclei (Figure ).
The interpapillary space contained cells varying in size from small neurocyte cells to large ganglioid cells (some of them with neuronal nuclear features) that stained positive for synaptophysin (Figure ).
The Ki-67 labeling index was low (Figure ).
There were scattered hemosiderin deposits observed but no vascular proliferation or necrosis. |
pmc-6505976-1 | A 62-year-old woman was referred to our neurosurgical outpatient service with abnormal sensation in her trunk, arms and legs. The patient had a past medical history of a gastric ulcer, a right ankle plating after fracture 20 years ago and a headlice infection 6 months before first presentation. She was a smoker, social drinker of alcohol and was not taking any regular medication. She lived alone and had been struggling to manage independently.
Since her symptoms commenced 3 years previously, the patient had presented to emergency department (ED) on 11 occasions. Her primary complaint was of dysaesthetic sensory symptoms including a feeling of water retention and a gel infiltrating the skin of her face, trunk, arms and legs, feeling there was something stuck on her skin and feeling her hair was stuck down. In the weeks before the onset of her symptoms, the patient started using an olive oil moisturising cream, to which she attributed her symptoms.
While dermatological examination was conducted, comprehensive neurological examinations were not documented during the first presentations to the ED, which focused on the patient’s facial dysaesthesia.
The patient was frustrated that her symptoms were repeatedly dismissed as delusional by the ED staff. She refused assessment by liaison psychiatry and mental health review by her general practitioner. The patient was felt to have capacity throughout all consultations. The patient was not taking any psychiatric medications.
Over time her symptoms progressed. She started to complain of back pain, multiple falls and episodes of her right leg giving way which had progressed to severely compromised walking and coordination. The patient also complained of episodes of urinary and faecal incontinence. This led to a lumbar MRI which ruled out cauda equina syndrome. In her final presentation before referral, she also complained of stiff legs, difficulty walking, difficulty passing urine, reduced manual dexterity and neck pain. A neurology assessment was finally sought and an MRI for suspected myelopathy was organised.
On presentation to our neurosurgical clinic, the patient’s complaint remained sensory dysaesthesia from her neck down, particularly affecting her hands and groins. She complained of her body feeling like a ‘wet gel-like substance’. In addition to the above symptoms, the patient also complained of a 3-year medical history of numbness and tingling in her upper limbs.
On examination in the neurosurgical clinic, the patient had hyperaesthesia from the neck down, most prominent in the hands and groins. The patient had reduced grip strength of 3/5, finger extension and abduction of 3/5, wrist flexion and extension of 3/5, elbow flexion of 4+/5, elbow extension of 4/5 and shoulder abduction of 4+/5 on the Medical Research Council power scale. Hip flexion was 3/5, with all other muscle groups in the lower limb at 4+/5. The patient had very brisk reflexes with pathological spreading in the upper and lower limbs. There was self-limiting clonus in the ankle bilaterally. Hoffmann’s and Babinski reflexes were positive bilaterally. There was a severe loss of coordination and balance. Gait was impaired; the patient required a frame to mobilise. The severity of the patient’s cervical myelopathy was scored as 1 (upper limb motor dysfunction) +3 (lower limb motor dysfunction) +1 (upper limb sensory dysfunction) +1 (sphincter dysfunction) =6 (severe myelopathy) on the modified Japanese Orthopaedic Association scale (mJOA). |
pmc-6506272-1 | An 83-year-old male ex-smoker presented with progressive worsening of shortness of breath and dry cough for three days. His past medical history was significant for sick sinus syndrome, status-post pacemaker placement in 2014, heart failure with a reduced ejection fraction (HFrEF), hypertension, diabetes mellitus with dermopathy, rectal cancer status-post colostomy, chronic obstructive pulmonary disease (COPD), benign prostatic hypertrophy, and gout. He reported associated rhinorrhea and malaise and had been using his albuterol inhaler at home with no relief. He denied any associated chest pain, palpitations, pre-syncope, or syncope. Physical examination was remarkable for bilateral DELC, more prominent in the left ear (Figure ). Vital signs were stable. An electrocardiogram (EKG) showed an atrial paced rhythm at 89 beats per minute. A chest x-ray revealed clear lung fields with minimal atelectasis. Labs were pertinent for elevated troponin and D-dimer; troponin peaked at 0.58. He was started on a heparin drip. He underwent computed tomography angiogram (CTA) of the chest which ruled out a pulmonary embolus. A transthoracic echocardiogram revealed an ejection fraction of 35% - 40%, Grade 1 left ventricular diastolic dysfunction, and abnormal septal motion consistent with a conduction abnormality. He subsequently underwent a coronary angiogram which revealed disease of the circumflex artery with a 30% lesion in the proximal segment, a 50% lesion in the distal segment, and a 50% lesion in the proximal segment of the obtuse marginal artery focal lesion) (Figure ). In view of the presence of non-obstructive CAD, he was started on appropriate medical therapy and discharged with a cardiology follow-up for medical optimization. |
pmc-6506274-1 | A 28-year-old male came to the emergency department, complaining of profound fatigue, chest pain on exertion, dizziness, diplopia, and headaches. He endorsed heavy marijuana and alcohol use. Physical exam elicited a thin man, poor dental hygiene, tachycardia, and a soft apical murmur.
Ophthalmic examination revealed esotropia of the left eye, diffuse retinal hemorrhages, and Roth spots. An electrocardiogram was read as normal. MRI revealed evidence of a stroke with a 4 mm lesion of the right periaqueductal gray (PAG) (Figure ). A complete blood count (CBC) showed a hemoglobin level of 1.12 g/dl (normal: 13.5-17.5 g/dl) and a platelet count of 16,000/µL (normal: 150,000-450,000). Repeat CBCs two and six hours later were 1.28 g/dl and 1.73 g/dl, respectively, while his repeat platelet count was 7,000/µL. The patient was emergently transfused, totaling six units of packed red blood cells (pRBC) and one unit of platelets over the next three days. He was also started on judicious iron supplementation due to a peripheral blood smear displaying severely microcytic and hypochromic red blood cells. After three units of pRBC, his presenting clinical symptoms, including his focal neurologic deficit of esotropia, began resolving. |
pmc-6506456-1 | We present the case of a 55-year-old female Caucasian patient trained as an occupational therapist who has suffered from chronic paranoid–hallucinatory schizophrenia since the age of 30. She continuously showed positive symptoms with superimposed exacerbations. At the age of 34, she was forced to retire early from her career due to her illness. Her delusions included the idea that she had sinned and needed to die, and she perceived diverse signs as confirmation of these delusions. She suffered from auditory hallucinations (voices from God, the devil, and her dead partner or mother), visual hallucinations (visions of angels), and a loss of self-boundaries (believing that other people could read her thoughts). Negative symptoms included a lack of motivation, flattened mood, and social withdrawal. Cognitive impairment has been observed since the onset of psychotic symptoms, with inattention and increasing deficits in working memory.
Intermittently, the patient abused alcohol (at least four beers per day) and benzodiazepines, but no illegal drugs. Her consumption of these substances increased during psychotic exacerbations with social withdrawal. The early death of her life partner reinforced this withdrawal. Since the onset of the disease, she had attempted suicide 10 times. Therefore, there were frequent inpatient stays in different psychiatric hospitals. Neither various neuroleptic treatments with average or high doses of aripiprazole, amisulpride, clozapine, haloperidol, perazine, pimozide, quetiapine, and risperidone, nor anticonvulsive treatment with valproate as an augmentation strategy led to full remission. Under different combination treatments, the described symptoms persisted at a reduced level.
At age 20, the patient developed clinical signs of HNPP. Initially, she was quickly fatigued and showed transient hypoesthesia of the left arm and foot. She developed transient foot dorsi-flexor paresis twice on the right side. The symptoms occurred after mechanical pressure on the corresponding body regions. In the further course of the disease, she developed transient left brachial plexus paresis at the age of 32 and again at the age of 35. When she was 35, genetic testing revealed a deletion on chromosome 17p12 involving the peripheral myelin protein 22 gene (PMP22), confirming the diagnosis of HNPP. The most recent neurological examination showed a discrete foot dorsi-flexor paresis on the right side (Medical Research Council score M4), absent Achilles tendon reflexes on both sides, slight pallhypesthesia of the lower extremity accentuated on the right side (5/8 on the right versus 6/8 on the left), and an ataxic and unsteady gait.
The patient’s developmental history was negative for in utero or birth complications, febrile convulsions, inflammatory brain diseases, and cerebral contusions. There was no evidence of any neurodevelopmental disorder. In the first two decades, the patient’s premorbid personality showed dependent traits. Her somatic medical history included only hypothyroidism, which was diagnosed at age 43. Her family history was positive for schizophrenia and HNPP. Her father’s half-brother suffered from schizophrenia. The patient’s older brother (transient hypesthesia of parts of one hand; side and explicit location unclear) and father (paresis of the shoulder abductors) potentially also suffered from HNPP (no genetic diagnostics performed, clinical reports not available). Her younger brother and her mother were healthy.
The serum, cerebrospinal fluid, and cerebral magnetic resonance imaging (cMRI) investigations did not show any evidence of an immunological cause for schizophrenia or PNPs. The electrophysiological tests revealed sensorimotor, demyelinating PNP (accentuated in the legs). Neurosonography showed bilateral enlargement of the median and ulnar nerve at typical sides of entrapment syndromes. Neuropsychological testing showed considerable deficits in working memory and a mild deficit in psychomotor speed. The electroencephalography (EEG) showed rare intermittent slowing. The cMRI showed generalized atrophy (Figure 1). Magnetic resonance spectroscopy (MRS) was performed in the dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex (dACC), and the pregenual anterior cingulate cortex (pACC) using a MEGA PRESS sequence (repetition time = 1,500 ms, echo time = 68 ms, flip angle = 90°) and the acquired spectra were quantified with the software LCModel. Glutamate concentrations in the dACC and pACC were relatively high and outside the 90% reference intervals. The myo-inositol concentrations in the pACC were relatively low and within the 90% reference interval (Figure 2). The DLPFC measurement displayed poor spectral quality and was therefore not analyzed. The diagnostic findings are summarized in Table 1.
MLPA (multiplex ligation-dependent probe amplification) analysis revealed a heterozygous deletion of the PMP22 gene on chromosome 17p12. To delineate the extent of this deletion, we additionally performed conventional karyotyping and array CGH (comparative genomic hybridization).
Conventional R-banded karyotypes from the patient were analyzed according to standard protocols with a resolution of approximately 500 bphs and revealed a structurally and numerically normal female karyotype (46,XX) in all 28 metaphases examined. Furthermore, the genomic DNA of the patient was examined by microarray analysis (CytoSureTM constitutional v3 array 180k; Oxford Gene Technology) according to the manufacturer’s instructions. After hybridization, the array was scanned with the SureScan microarray scanner (Agilent); the results were analyzed using CytoSure interpret software v.4.9 (Oxford Gene Technology) and the Genome Reference Consortium human genome GRCh37 (hg19). Molecular karyotyping revealed a heterozygous deletion of approximately 1.33 Mb (125 contiguous oligonucleotides) out of the chromosomal region 17p12 (karyotype after the International System for Human Cytogenetic Nomenclature, 2016: arr[GRCh37] 17p12(14111972_15442257)x1). The deletion encompasses i.a. the genes COX10, HS3ST3B1, PMP22, TEKT2, and CDRT4. A deletion of that extent in 17p12 is found in nearly 80% of patients with HNPP (). Further chromosomal deletions or duplications that might have etiologically contributed to our patient’s disease were not detected.
The patient’s psychiatric symptoms were compatible with paranoid–hallucinatory schizophrenia (ICD-10: F20.0). The PNPs in combination with the deletion of the PMP22 gene led to the diagnosis of HNPP (ICD-10: G60.0). Due to the potential secondary schizophrenia in the context of HNPP, a psychotic disorder with delusions due to a known physiological condition might ultimately be diagnosed (ICD-10: F06.2). |
pmc-6506511-1 | A 67-year-old female with a medical history of poorly controlled diabetes mellitus transported to the emergency room with hematemesis and disordered consciousness. She had suffered from nausea and epigastralgia for 2 days. The patient’s general status was shock evidenced by vital signs, and she did not respond to rehydration. Laboratory findings showed blood glucose of 470 mg/dL; arterial blood gas with a pH of 7.2, PCO2 of 25.2 mmHg, HCO3 of 9.9 mEq/L, and PO2 of 169 mmHg with an anion gap of 24.3 mEq/L; and positive urinary ketones and glucose. These findings were consistent with the diagnosis of diabetic ketoacidosis. After intubation, emergency endoscopy revealed black pigmentation in the entire esophageal mucosa (Fig. a, b). A CT scan revealed the circumferential edematous thickening of the esophageal wall with slight pleural effusion (Fig. a). However, no obvious sign of perforation, such as free air in the mediastinum, was observed. AEN was diagnosed from these findings, and antibiotics, glycemic control, proton pump inhibitor (PPI), and plasmapheresis were started. The patient gradually stabilized and was extubated on day 5. However, she still had a fever, and the chest X-ray revealed the accumulation of pleural effusion. On day 7, esophageal perforation was suspected from the significant increase of the right pleural effusion and free air in the mediastinum on CT scan (Fig. ).
Emergency thoracoscopy was performed in the left semiprone position with differential lung ventilation and artificial pneumothorax. Significant pleural effusion with pus and perforation of the esophagus was observed (Fig. ). We resected the transmural necrotic thoracic esophagus and placed drainage tubes at the anterior side of the thoracic cavity, at the posterior mediastinum, and above the diaphragm. After transitioning the patient to the supine position, the esophagus was resected at the cardia of the stomach and the esophageal hiatus was closed. Then, an enterostomy tube was inserted from the upper jejunum, and the drainage tube was placed at the stump of the stomach. Finally, we constructed an esophagostomy with the residual cervical esophagus in the supraclavicular area. The total duration of the operation was 6 h and 33 min. On the resected specimen, mucosal necrosis was found only on the squamous epithelium, with a perforated area in the middle to lower thoracic esophagus (Fig. a). Pathological findings revealed necrosis of the esophageal mucosa, while no signs of inflammation or ischemia were found on the gastric mucosa of the esophagogastric junction (Fig. b).
The patient recovered generally well, except that the severe stricture of the residual cervical esophagus had developed a month after the operation. The stricture was endoscopically dilated repeatedly. However, the dilation was not successful enough, and 7 months after the initial operation, endoscopic balloon dilation (EBD) was required once a week (Fig. ). Nine months from the first operation, resection of the stricture was performed using cervical esophagectomy accompanied by tracheotomy. Reconstruction was performed with free jejunum interposition between the hypopharynx and gastric tube through the anterior thoracic route (Fig. a). We used the superior thyroid artery and internal jugular vein for feeding artery and drainage vein of the free jejunum (Fig. b). No postoperative complications occurred, and she was transferred to rehabilitation therapy to continue swallowing rehabilitation on the 37th day after the operation. Her enterostomy tube was removed 3 months after the operation; she is now eating well and doing fine after all operations and therapy. |
pmc-6506557-1 | An 80-year-old Puerto Rican man with asthma and chronic obstructive pulmonary disease (COPD) was referred to our medical center's otolaryngology office for 2 months (day −60) of hoarseness and sensation of a lump in the throat. He didn't have fever, weight loss, night sweats, or neurological symptoms (day 0). He had chronic cough productive of yellowish sputum and dyspnea requiring a fluticasone-salmeterol (500/50 mcg) one puff twice daily over 10 years and intermittent COPD exacerbations requiring a short course of oral prednisone every 2–3 months for a couple of years (day −730 to 0). The patient quit smoking 40 years ago after a 20-pack-year of cigarette smoking. He did not have a history of any serious infections as a child.
The patient was noted to be well-appearing with unremarkable physical examination other than mild scattered crackles and wheezes on lung auscultation (day 0). A flexible laryngoscopy and stroboscopy, however, revealed erythema and edema of the vocal folds, whitish mucopurulent material coating the endolarynx, and mucosal irregularity and ulceration of the vestibular folds extending upward along the laryngeal surface of the epiglottis (day 0) (). Empiric 1–2 week courses of oral clotrimazole and nystatin for clinically suspected laryngeal candidiasis, and amoxicillin-clavulanate did not alleviate his symptoms or improve his laryngeal findings. Thereafter, microbiology testing and tissue biopsy were pursued (day +49). Bacterial, acid-fast bacilli (AFB), and fungal cultures of whitish mucus did not yield any organisms. Histopathologic assessment revealed three small fragments of biopsied vestibular folds lesions showing squamous mucosa with ulceration and inflamed granulation tissue, admixed with variably sized round encapsulated yeast forms fungal organisms. These yeast forms were positive for hematoxylin and eosin, Grocott-Gomori methenamine-silver (GMS) and mucicarmine stains, consistent with Cryptococcus species (). Immunohistochemical stain, and molecular test confirmed a diagnosis of Cryptococcus neoformans. Cryptococcal antigen titer in the serum was 1:20 (day +70).
The patient recalled cleaning up massive pigeon droppings on his terrace 3 months prior to the onset of his symptoms (day −150). His initial white blood cell (WBC) count was 13.1 × 109/L (neutrophil 8.9; lymphocyte 2.8; monocyte 1.0) (day 89). Blood for AFB and fungal cultures were negative (day +92). Cerebrospinal fluid analysis revealed no evidence of meningitis (day +92). Comparing prior CT scans over 3 years, CT of the chest showed new thickening and narrowing of the distal trachea with extensive secretions and impaction of multiple bilateral lower lobe branch bronchi and stable mild bronchiectasis and a few micronodules (day +93). Subsequent bronchoscopy demonstrated a nodular lesion in the narrowed distal trachea, which was biopsied (day +97). Histopathologic exam of the biopsied samples showed tracheal mucosa with focal ulceration, inflammation, fibrosis and rare yeast forms, compatible with Cryptococcus species. Multiple respiratory cultures obtained from the bronchoscopy and expectorated sputum specimens were positive for MAI, but Cryptococcus was not detected (day +97). An immunodeficiency work up was performed (day +70 to +133), including HIV antigen/antibody, lymphocyte subsets (T-cells, B-cells, natural killer cells), immunoglobulin levels, complement levels, neutrophil oxidative burst assay, MBL level, anti-granulocyte-macrophage colony-stimulating factor (anti-GM CSF) autoantibodies, and Mendelian susceptibility to Mycobacterial disease panel: all were unremarkable, but MBL level was significantly low at 6 ng/ml.
The patient was placed on fluconazole 400mg daily and a salmeterol inhaler instead of a fluticasone-salmeterol inhaler to avoid inhaled corticosteroid (day +91). Three months after fluconazole initiation (day +181), the patient's hoarseness resolved with near complete resolution of laryngeal findings. At five months after fluconazole initiation (day +241), his laryngoscope exam had completely normalized. Due to persistent cough productive of thick respiratory secretions and repeatedly positive MAI from respiratory cultures, the patient was started on azithromycin, rifampin and ethambutol to target MAI at 3–4 months after fluconazole initiation (day +190). Fluconazole trough level was measured due to interaction between fluconazole and rifampin, which was well above the general minimal inhibitory concentration (day +300). A follow-up CT of chest revealed a new occlusion of right middle lobe bronchus and persistent tracheal stenosis, for which the patient underwent balloon dilatation and cryotherapy in the distal trachea (day +239). Eventually, a tracheal stent was placed for non-resolving tracheal stenosis resulting in improvement of tracheal stenosis (day +342). Serum cryptococcal antigen became undetectable after 10–11 months of fluconazole therapy (day +401). The patient completed a total 12 months of fluconazole therapy (day +456) and is planned for 12 months of MAI therapy after sputum AFB conversion. |
pmc-6506910-1 | The patient was a 79-year-old woman who had first become aware of leg edema several
years earlier. She presented to our clinic with edema below the knee (). Her lower extremity
lymphedema (LEL) index (calculated by summation of the squares of the circumferences
for five areas in each lower extremity divided by the body mass index) was 179 on the right and 173 on the left. There were varicose veins along the
medial side in the edematous leg. Her clinical disease severity was graded as C3
using the revised Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification.
Duplex ultrasound scanning was performed using a 7.5-MHz transducer and the
Noblus™ Ultrasound Diagnostic System (Hitachi Aloka, Tokyo, Japan) with the
patient in the standing position. Reflux longer than 2.0 s was observed along
the entire length of the GSV in both the thigh and lower leg regions after a
provocative maneuver using manual compression of the calf. Ultrasonography did
not reveal venous thrombosis. The varicose veins were stripped successfully from
the ankle to the groin bilaterally ().
Clinical disease severity was graded as stage 2 using the Campisi clinical
staging system for lymphedema. Lymphatic function was investigated to verify lymphedema and to confirm
the status of lymphatic flow before and after stripping. The procedure was
carried out by injecting 0.1–0.2 mL of ICG dye (Diagnogreen 0.5%; Daiichi
Pharmaceuticals, Tokyo, Japan) subcutaneously into the first interdigital space
and into the posterior lateral condylar region. ICG images were then acquired
using a photodynamic eye system (Hamamatsu Photonics, Hamamatsu, Japan). The
patient lay still in the supine position while repeating dorsiflexion and
plantar flexion of the toes and ankles at her own pace during measurement of
transit time. The purpose of repeating dorsiflexion and plantar flexion of the
toes and ankles was to reduce the excessive delay of flow, which often occurs in
running flow over the ankle joints. When flow was too slow, passive movement of
the ankle or knee was applied to confirm if flow was interrupted or not; this
had almost no effect on the results of ICG lymphography. Transit time was
defined as the time required for uptake of ICG at the groin. Lymphatic flow was observed in the right leg along the medial side from
the foot to the groin immediately within 3 min of injection of ICG; however,
lymphatic flow was blocked and dilatation of the lymphatics was subsequently
absent beyond the middle part of the left lower leg even with passive movement
at the ankle and knee for over 10 min (). There were no changes in the findings on
ICG lymphography in the 3 h after injection of ICG. The right leg showed a
linear pattern, but the left leg showed less enhancement pattern ().
Based on these findings, we made a diagnosis of bilateral varicosity of the GSV
with left-sided lymphedema. Stripping under lumbar anesthesia was planned first
with subsequent lymphaticovenular anastomoses.
Ligation and division of the tributaries at the saphenofemoral junction and
dissection of the GSV were performed at the level of the ankle. The GSV between
the groin and ankle was subsequently stripped on both sides under tumescent
local anesthesia to minimize bleeding as much as possible. No perforator veins
in the lower leg were divided. Sclerotherapy was not performed perioperatively.
Limb compression was performed for one night to prevent postoperative
hemorrhage. |
pmc-6507031-1 | A 21-year-old female was admitted to our hospital complaining of fever and fatigue for 2 months. She was an editor and had been in good health until 2 months ago when she developed a spiking fever of 39–40 °C, dry cough, night sweats and fatigue. She went to a local hospital, and a complete blood count (CBC) revealed only mild anaemia (Table ). She was diagnosed with an “upper respiratory tract infection”. Cefprozil was administered, but her symptoms gradually worsened, and a growing mass, which was painful, was found on the right side of her neck. She reported no arthralgia, rash, weight loss or relevant family history.
Her physical examination upon admission revealed scattered rales on the right lung, splenomegaly and enlarged lymph nodes that had coalesced and were palpated in her right cervical region. The initial laboratory investigation showed peripheral pancytopenia (white blood cells (WBC) 2.28*109/L, HGB 87 g/L, PLT 71*109/L, Table ), elevated liver enzymes (ALT 192 U/L, AST 139 U/L, LDH 554 U/L) and hyperferritinaemia (Fer 4090 ng/ml). Natural killer (NK) cell activity was tested via a flow cytometry-based assay previously reported by Zhang et al. and was found to be reduced []. Haemophagocytosis was found in the bone marrow aspirate (Fig. ). Initial serological investigations for common pathogens and autoimmune diseases were negative (Table ). A chest CT scan revealed bilateral nodules and right pleural effusion (Fig. ), but Gram staining, acid-fast staining and mycobacterial culture of sputum were negative. An ultrasound-guided puncture was performed on her right cervical lymph nodes. Ziehl-Neelsen staining revealed acid-fast bacilli, and further nucleic acid probes identified M. intracellulare. Histology from the biopsied tissue showed inflammatory necrosis and calcification without evidence of malignancy. Then, M. intracellulare was cultured from her peripheral blood and lymph node tissue. We suspected that the patient might have autoantibodies against interferon-γ, which led to her immunosuppressive state and susceptibility to NTM infection. Unfortunately, serum testing for interferon-γ autoantibody was not available in our hospital.
A regimen containing clarithromycin (500 mg BID po), rifampicin (450 mg QD po), ethambutol (750 mg QD po) and amikacin (0.4 g QD iv) was started to treat the disseminated M. intracellulare infection. HPS was also diagnosed according to the HLH-2004 criteria, and prednisone 60 mg QD po (1 mg/kg/d) was given to control the inflammation.
Her temperature soon became normal. Prednisone was gradually tapered (60 mg QD*2 weeks→40 mg QD*2 weeks→20 mg QD*2 weeks→↓5 mg/2 weeks until stop), and amikacin was stopped after 1 month, while clarithromycin, rifampicin and ethambutol were continued. She was in remission, and her cervical lymph nodes were unpalpable with normal CBC at the 6-month follow-up visit. The patient was then lost to follow-up. |
pmc-6507051-1 | Five days prior to hospital admission, the 73-year old male suffered from mucous congestion, a swollen throat, fever and shivering. He subsequently developed severe leg-weakness, back pain and jaundice as well as psychiatric symptoms with delusion and hallucination while his fever worsened with a body temperature of 39.8 °C. Myalgia did not occur initially. After consulting his primary care physician, he was immediately transferred to the emergency department (ED) at another hospital.
Apart from a history of depression and Helicobacter pylori – gastritis a few years ago, his medical history was unremarkable with no other preexisting conditions. There was no recent travel nor alcohol consumption. The only regular medication was 40 mg of Citalopram daily. The physical examination revealed jaundice and minor petechiae at the lower legs. The abdomen was slightly distended with pain after palpation in the right upper quadrant. Peristaltic sounds were normal. Examination of the heart and the lungs were unremarkable. Conjunctival suffusion was not found.
Initial blood analysis revealed leukocytosis (13.2/nl), thrombocytopenia (23/nl) as well as elevated values for C-reactive protein (CRP, 174.6 mg/l), procalcitonin (PCT, 10.0 ng/ml, cutoff < 0.5 ng/ml), lactate dehydrogenase (LDH) (312 U/l), creatinine (2.95 mg/dl, clearance 20 ml/min/1.73qm), aspartate aminotransferase (AST, 55 U/l), bilirubin (14.9 mg/dl, direct bilirubin 11,72 mg/dl) and lipase (2417 U/l). Sodium (125 mmol/l) and potassium (3.18 mmol/l) were reduced, hemoglobin (Hb), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) were normal. An overview of selected initial laboratory values can be found in Table . Urine analysis revealed nitrite positivity with leukocytes, proteinuria, erythrocytes and bilirubin. An initial X-ray of the chest showed no relevant pathologies.
Due to acute septic pancreatitis and acute kidney injury he was transferred to the intensive care unit (ICU). Antibiotic treatment was started with ampicillin/sulbactam. Although no cholestasis or gallstones were found in an initial abdominal ultrasound, a biliary pancreatitis with sepsis was suspected. Thus, an endoscopic retrograde cholangiopancreatography (ERCP) was performed 1 day after his primary presentation at the ED. This procedure revealed a normal duodenum, a swollen papilla vateri and only minor spontaneous biliary drainage was observed. Intrahepatic bile ducts and the common hepatic duct were not dilated. While preparing for the endoscopic procedure, the respiratory and hemodynamic condition of the patient worsened. Consequently he was intubated, commenced on a noradrenaline infusion, and the antibiotic treatment was escalated to meropenem.
A chest CT scan demonstrated bilateral pulmonary infiltrates and small bilateral pleural effusions. Microbiological analysis of blood cultures was negative at all time points tested. A screening for ANA and ANCA was also negative.
The following day, the patient was transferred to our university medical center ICU with sepsis and acute pancreatitis, acute kidney failure and acute respiratory distress syndrome (ARDS).
In our ICU, antibiotic treatment with meropenem and catecholamine treatment with noradrenaline were continued. Blood cultures were taken repetitively and a sample of the tracheal secretion was obtained. After 5 days, weaning from artificial respiration and noradrenaline was possible and the patient was transferred to our gastroenterological ward. The physical examination revealed a slight transient rash of his back. We performed further investigations regarding the etiology of the patient’s condition. A stool test for Clostridium difficile antigen was negative. Further sampling by blood cultures, tracheal secretion and urine-analyses showed no growth of any bacteria. A screening for MRSA was negative, as were serologic tests for Hepatits B, Hepatitis C, mumps and Epstein-Barr virus. Acute liver failure with jaundice, hemorrhagic diathesis with purpura and petechiae combined with acute kidney injury accompanied by an odd transient macular, erythematous rash directed to serologic testing for leptospirosis. It revealed strong positive IgG and IgM antibodies. While leptospirosis PCR in the blood was negative, analysis of the tracheal secretion taken during his stay on the ICU revealed the presence of Leptospira interrogans DNA. Urine analysis performed at the same time however remained negative for leptospirosis DNA by PCR. PCR was performed by the Institute of Microbiology and Hygiene of the University of Freiburg, Germany, which is accredited by the DAkkS (Deutsche Akkreditierungsstelle, Berlin, Germany) for leptospira PCR for probes of both sterile and non-sterile origin.
An ultrasound of the patient demonstrating prominent edematous pancreas can be found in Fig. .
The patient was discharged 18 days after his atypical presentation at the ED with normalized lab values. |
pmc-6507060-1 | A 49-year-old Indian man presented with progressively increasing swelling in his left hand of 2 months’ duration, along with pain and redness of overlying skin (Fig. ).
There was no history of antecedent trauma. A detailed history revealed that he was diagnosed as having osteosarcoma of his right leg 3 years previously, for which he had an operation (wide local excision) and had received chemotherapy (MTX, doxorubicin), leading the tumor to resolve. Following this, sequential whole body PET scans were performed, which revealed no evidence of residual disease in his right leg or any tumor elsewhere. The remaining medical history, family history, and psychosocial history were unremarkable. On examination, the overlying skin was stretched and showed redness, and the swelling was hard in consistency. An X-ray showed a soft tissue lesion (Fig. a) Contrast-enhanced computed tomography (CECT) showed a soft tissue mass lesion of size 3.8 × 3 cm, with peripheral enhancement and central necrotic areas in radial palmar soft tissue overlying second metacarpophalangeal region with no obvious bony osteolysis (Fig. b).
Possibilities of acute abscess, resolving hematoma, or aggressive soft tissue mass lesion were suggested. The aspirate from the swelling was sent for culture sensitivity which was sterile. An incision biopsy was performed. Hematoxylin and eosin (H&E) sections showed a tumor with tumor cells arranged in sheets and vague nodules, separated by large areas of hemorrhage and necrosis. The tumor cells were large, showing a high degree of pleomorphism and atypia, varying in shape from epithelioid to spindle to polygonal, and had eosinophilic cytoplasm with cytoplasmic vacuolation. Nuclei had irregular nuclear membranes and prominent nucleoli. A large number of atypical mitoses were seen. Numerous variable-sized blood vessels were seen showing presence of tumor emboli (Fig. a–c).
An immunohistochemistry (IHC) panel was put up, comprising cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, osteopontin, smooth muscle actin (SMA), desmin, leukocyte common antigen (LCA), and cluster of differentiation (CD) 99 and CD 34. The tumor cells were positive for CK, EMA, osteopontin, and vimentin (Fig. a–c). They were negative for SMA, desmin, LCA, S-100, and CD 99 and CD 34, ruling out leiomyosarcoma, rhabdomyosarcoma, lymphoma, Ewing’s sarcoma, and angiosarcoma, respectively. Furthermore, on extensive sampling, sections from the tumor showed presence of osteoid (Fig. d). Previous radiology (Fig. ) and histopathology were also reviewed (findings were similar to that of the present lesion) and the diagnosis of osteosarcoma was confirmed.
Based on history, radiology, morphology, and IHC, a final diagnosis of extraskeletal (soft tissue) epithelioid osteogenic sarcoma of the left hand occurring as a metachronous tumor 3 years after diagnosis of primary osteosarcoma in the right leg (Amstutz type IIIb) was given. A whole body PET scan revealed no evidence of viable residual/recurrent disease at our patient’s right leg; however, heterogeneously enhancing soft tissue mass lesion in thenar region of his left palm causing bony erosion of underlying second metacarpal bone, heterogeneously enhancing irregular mass lesion in upper lobe of his right lung, along with bilateral pulmonary nodular lesions were suggestive of metastatic deposits. Prior to the discovery of the metachronous tumor, his lungs and skeleton had been continually free of disease, and the lung lesion was attributed to the metachronous tumor. He underwent wide local excision of the palm tumor. This was followed by chemotherapy (MTX, doxorubicin, cisplatin) for the hand as well as the lung deposits. He has been on follow-up for the past 8 months, is still under follow-up, and is presently doing fine (Additional file ). |
pmc-6507100-1 | In 2006, a 13-year-old black female presented to Dr. Mário Gatti Municipal Hospital with a complaint about a volume augmentation on the left side of her mandible for 3 months. Her medical history was not contributory. Panoramic radiography revealed a well-delimited radiolucent lesion circumscribing the tooth germ of the third molar (). The clinical suspicion was dentigerous cyst, odontogenic keratocyst, or ameloblastoma.
Two incisional biopsies followed by an excisional biopsy were performed, and the specimens were fixed in 10% buffered formalin. Paraffin sections were prepared for light microscopy using routine procedures. The sections were stained with hematoxylin and eosin. At that time, the first histologic diagnosis for incisional biopsy was dental papilla, while the histologic diagnoses for the other biopsies were inconclusive and compatible with a developing tooth. In 2014, the description of new odontogenic entity called POT leads us to revise the present case, which exhibited histologic similarities with the cases described by Mosqueda-Taylor et al. [].
Histologic analysis revealed a fragment of loose connective tissue covered with the epithelium exhibiting predominantly a columnar morphology (). In the connective tissue, areas with a great number of cells showing a morphology ranging from fusiform to stellate morphology were noticed (). On the other hand, regions with low cell density and myxoid appearance were also observed in the connective tissue (). The epithelium was characterized by the presence of columnar cells. In some areas, the columnar cells were covered by a stratified squamous epithelium, which was interpreted as similar to the outer enamel epithelium of the enamel organ (). Calcified areas and/or odontogenic epithelial islands or cords were not detected in any part of the specimen. These histologic findings rendered the diagnosis of POT. |
pmc-6507114-1 | A 50-year-old African American female presented with a three-week history of intractable headache, confusion, vertical binocular diplopia, photophobia, and difficulty with balance. Examination revealed best corrected visual acuities of 20/25 in the right eye (OD) and 20/20 in the left eye (OS) with intraocular pressures (IOP) of 14 mmHg in both eyes (OU). No afferent pupillary defect was noted, extraocular motility (EOM) was full OU, and confrontational visual fields were full OU. Anterior segment examination in both eyes was unremarkable. Funduscopic examination of both eyes revealed grade-four optic disc edema, blurring of optic disc margin, and obscuration of vasculature of the optic nerve. Preretinal and intraretinal hemorrhages were present in both eyes, largely concentrated in the peripapillary retina, but extending to the mid-peripheral retina (Figures and ). Optic nerve swelling was confirmed on optical coherence tomography (OCT) of the retinal nerve fiber layer (Figures and ). Fluorescein angiography revealed hyperfluorescence of the optic disc OU (Figures and ).
Computed tomography of the head, magnetic resonance imaging of the brain, and magnetic resonance venography of the brain were unremarkable and had no evidence of intracranial mass, hemorrhage, or ischemia. Cerebrospinal fluid (CSF) analysis revealed an opening pressure of 30 cm H2O, 77 white blood cells/mm3 with 94% lymphocytes, 93 mg/dL protein, and 73 mg/dL glucose. Bacterial and fungal cultures of the CSF were negative. CSF studies for Lyme, syphilis, herpes simplex virus, and West Nile virus were unremarkable. A limited panel consisting of laboratory studies for enterovirus, syphilis, ANA, and p-ANCA was negative. A respiratory viral panel for adenovirus, cytomegalovirus, influenza, parainfluenza, rhinovirus, and respiratory syncytial virus was negative on Polymerase Chain Reaction testing. Based on the patient's presentation and cerebrospinal fluid findings, she was diagnosed with viral meningoencephalitis. She was monitored as an inpatient with conservative management. During the hospital course, the patient noted improvement in her double vision and headaches. A repeated lumbar puncture 5 days later revealed opening pressure of 4 cm H2O, 38 white blood cells/mm3, 75 mg/dL protein, and 57 mg/dL glucose. The patient was subsequently discharged from the hospital.
Follow-up examinations with serial OCT of the optic nerve showed continued progressive improvement in disc edema (Figures –) along with complete resolution of papilledema and peripapillary hemorrhages (Figures –). Mild residual pallor of both optic nerves was observed at the end of one year. OCT revealed borderline temporal thinning of the right optic nerve. The left optic nerve had borderline temporal thinning, borderline superotemporal thinning, and inferotemporal thinning. The findings of persistent disc pallor and inferotemporal nerve fiber layer thinning on OCT were consistent with the persistent visual field deficit documented on Humphrey visual fields (Figures –). |
pmc-6507115-1 | A 41-year-old male patient with no comorbidities except history of alcoholism—consumption of distillates daily in the last twenty-five years—and smoking (60 pack-years) presented with dysphonia and right cervical lymphadenopathy in October 2017. The symptoms worsened to progressive dysphagia and odynophagia and emergence of small subcutaneous implants in the right flank. He underwent a digestive endoscopy in November 2017, which showed a 5-centimeter lesion from 20 centimeter of the upper dental arch, compatible with a well-differentiated squamous cell carcinoma on the pathological report.
After initial evaluation by the surgical staff, the patient was referred to exclusive treatment with clinical oncology and radiotherapy, since the tumor was not amenable to curative surgery. The staging computed tomographies demonstrated supraclavicular, mediastinal, paratracheal, infracarinal, and cervical bilateral lymphadenopathy, in addition to neoplastic implants on the right flank and right hemithorax and retroperitoneal and pleural nodules, as well as right fourth rib osteolysis. At this time, a biopsy in one of the subcutaneous implants located in the right flank was performed, confirming metastasis from esophageal squamous cell carcinoma () and immunohistochemistry (IHQ) was also performed, whose morphological findings were compatible with keratinizing epidermoid carcinoma infiltrating adipose tissue positive for p63/4A4 and cytokeratin cocktail.
In February 2018, the patient started his chemotherapy treatment with weekly paclitaxel and carboplatin with concomitant radiotherapy. Although metastatic, we chose this approach for a better response due to the bulky cervical disease, which engendered pain and discomfort.
Two months after beginning his treatment, the patient developed an intense lumbar and right thigh pain, associated with walking impairment. After a medical visit, hospitalization was chosen in order to evaluate the clinical etiology. A tomography was performed, and it showed a 38 mm right paravertebral expansive lesion on the L5 level, infiltrating the psoas muscle, lesions in soft parts of the left paramedian dorsal region, worsening of the armpit and right flank subcutaneous nodules (Figures and ), and multiple lymph node, bone, and pulmonary metastases.
Since the radiologic changes would justify the symptoms reported by the patient, palliative radiotherapy was indicated. However, the patient became drowsy and confused because of malignant hypercalcemia (serum calcium of 15,5 mg/dl). Altered mental status and elevated serum calcium persisted despite hyperhydration and administration of zoledronic acid. Few days later, he developed aspiration pneumonia followed by pulmonary focus sepsis.
The septic condition, as well as hypercalcemia, proved to be refractory to the proposed treatment. Considering the advanced disease, clinical intractability, and poor-performance status, exclusive palliative care was chosen. The patient died two and a half months after beginning his treatment. |
pmc-6507120-1 | A 42-year-old male, nonsmoker, with medical condition significant for hypertension presented to the emergency department after a fall followed by two episodes of seizures. On presentation physical examination was notable for altered level of consciousness and mild symmetrical decrease in power of 4/5 in all four limbs. Laboratory workup including complete blood count, electrolytes, coagulation panel, lipid profile, urine, and serum drug screen was unremarkable. CT scan head revealed a 1.5 cm left temporoparietal lobe intraparenchymal hemorrhage with surrounding edema as shown in (). As part of the diagnostic workup, an ECG was also performed on admission which was normal. The patient was admitted to the neurointensive care unit (NICU) for further management. A computerized tomography angiogram was performed, which showed early draining veins at the site of the lesion, suspicious for an underlying vascular malformation. Subsequently a cerebral angiogram was performed which confirmed the presence of an AVM underlying the hemorrhage (). A partial embolization of the AVM was performed, and the patient was boarded for surgical resection ().
On day 3 of admission, the patient complained of sudden-onset chest pain. He described it as left sided, retrosternal, sharp, nonradiating pain, worsened when lying down on left side, lasted 2-3 minutes and then resolved spontaneously. It did not recur however prompted an ECG which showed sinus rhythm with nonspecific ST segment elevation in leads V3-V6 (). Cardiology was consulted who deemed the ECG changes as J point elevation suggestive of benign early repolarization and not a true acute coronary event. A high sensitivity cardiac troponin assay done immediately and repeated two times at 6 hours and 12 hours from the onset of symptoms remained negative (<0.017 ng/ml; normal value <0.057 ng/ml). A transthoracic echocardiogram (TTE) performed later that day revealed no regional wall motion abnormalities or left ventricular dysfunction. The next day, patient was taken for craniotomy and surgical resection of the AVM (). The surgery was uneventful. A follow-up ECG on the postoperative day 1 revealed pronounced ST elevation with new T wave inversions (in leads V2-V6) highly suggestive of acute STEMI (). The patient was completely asymptomatic with no chest pain or other cardiac symptoms. Serial estimation of high sensitivity cardiac troponin was again negative (<0.017 ng/ml) and a repeat TTE was unremarkable. Given these findings and the absence of the symptoms, no intervention was done and he was monitored in the NICU.
The patient did not have any further untoward event(s) and continued to do well postoperatively with normalization of his ECG changes over the next 48 hours (). He improved neurologically and was transferred out of the ICU on day 7. He was subsequently discharged on day 12 with home health physical therapy, neurosurgery, and cardiology follow-up appointments. An exercise stress test was eventually performed 3 months' after discharge which did not reveal any evidence of coronary artery disease. |
pmc-6507130-1 | A 41-year-old non-smoker obese female patient was examined at the Department of Neurology and the Center for rehabilitation. Relevant history of the patient is summarized on a timeline in Fig. . She showed an onset of neuromuscular disorders during early childhood with a delay in motor and written language development. She had a hard time to complete physical exercise at school and always finished last. There was nothing really alarming in terms of muscle disorder until her first pregnancy at the age of 33 during which she experienced shortness of breath (dyspnea) at the 7 months of gestation and showed signs of weakness of lower limbs afterwards. At the age of 34 she showed worsening of breath symptoms, suffered from sleep apnea and started using a mechanical ventilation machine. Alarming symptoms of skeletal muscle disorders occurred immediately after delivery with progressive but rapidly incapacitating weakness of lower limbs. This worsened during the 3 following years, a period during which she first started being unable to get up by herself and then was unable to climb stairs. At the age of 37, she started to use a cane, then a walker for her daily walking needs. At the age of 39, she started using a wheelchair to move outdoors. Despite these signs of progressive muscle weakness, she never had a thorough neuromuscular investigation. It was wrongly thought that her health problems, in general, was mainly related to being overweight. At the age of 41, she had four episodes of lower limb paralysis during which she was completely unable to move her legs and support her weight. She did not seek medical consultation for the first three episodes. For the fourth, she was admitted to the emergency room (ER) and first referred to the Department of Neurology and then to the Center for Rehabilitation.
The family history showed that her mother died at the age of 66 from a heart attack associated with non-compaction cardiomyopathy. There is nothing remarkable in terms of muscle disorders in her father, brother, and sister. However, her only daughter, now at the age of 11, shows signs of muscle disorders with congenital muscular torticollis, excessive growing pains as well as underdeveloped muscles in half of the body.
Physical examinations conducted following her admission to the ER at the age of 41 showed normal tone/bulk of the arm muscles. However, muscles in shoulders and upper and lower limbs showed bilateral weakness. Deltoids, biceps and triceps showed moderate weakness with MRC scale of 3/5. Fine finger movements were intact. There was no pronator drift. In the lower limbs, all muscles examined showed the same severity of weakness (2/5) except quadriceps which showed mild weakness (4/5). Hip flexors were extremely weak (1/5); hip abductors and adductors were mildly weak (4/5). Knee extensors and flexors were moderately weak (3/5). Dorsiflexion of feet was severely weak (2/5). Plantar flexors were severely weak (2/5). Deep tendon reflexes were 2+ in the arms, absent in the patella and Achilles. The toes were down-going. No sensory deficit was observed. No sign of dysphagia or involvement of ocular muscles was observed.
Additional physical examination conducted during the 2-year follow-up (at the age of 43) showed no worsening of muscle strength. However, this brought new information about the weakness of other muscles, notably in the shoulders, with extremely weak abductors and flexors (1/5). The patient showed decreased perception of vibration in the lower limbs. She reported that she experienced occasional dysphagia.
Electrophysiological exams showed normal nerve conduction velocities for upper and lower limbs, with all SNAP and CMAP amplitudes in the range of normal values. However, needle EMG revealed a tendency of myotonic potentials, generated by needle insertion. Right deltoids, biceps and ulnar-innerved first dorsal interosseus muscles showed myotonic potentials as well. The right tibialis anterior showed 2+ polyphasic motor unit potentials with myotonic potentials. The right medial gastrocnemius, vastus medialis and vastus lateralis showed myotonic tendencies as well.
Examination of muscle biopsy of left quadriceps showed features of an end-stage process, consistent with a severe, chronic myopathy. There are scattered clusters of viable muscle fibers which showed myopathic features in the form of a marked variation in fiber size and numerous internal nuclei. In addition, there are scattered fibers with abundant intrasarcoplasmic vacuoles (Fig. a, b). Given we could not clearly observe the presence of hyaline bodies on H&E staining we decided to proceed with p62 immunostaining, a well-known technique for revealing the presence of inclusion bodies []. Immuno-histochemical detection of p62 was performed on a Leica Bond III automated stainer. Following digestion in a low pH citrate solution, sections were incubated in a primary mouse monoclonal anti-p62 antibody, diluted 1:50 (BD Transduction Laboratories Catalog Number 610833). Detection of bound antibody was achieved using the Leica Bond Polymer Refine Detection kit, comprising the secondary antibody, the substrate chromogen DAB (3,3′-Diaminobenzidine tetrahydrochloride hydrate) and the Hematoxylin counterstaining solutions. Immunostaining for p62 revealed, in a proportion of the surviving muscle fibers, diffusely distributed, small intermyofibrillar dots or, more commonly, larger central or eccentric sarcoplasmic inclusion bodies (Fig. c, d). Examination of heart function using Holter ECG monitor carried out following her admission to the ER showed no clinically significant implication of cardiac involvement. However, the patient complained about repeated episodes of oppressive chest pain during the following years. Additional examination conducted during the 2-year follow-up showed signs of cardiac involvement with bradycardia of 58 beats per minute.
Regarding respiratory involvement, the patient suffered from dyspnea since the age of 34. Examination of lung function conducted following her admission to ER and during the follow-ups showed worsening of her respiratory condition. Spirometry test conducted at the age of 44 showed a very weak pulmonary function, with forced vital capacity (FVC) of 27% and forced expiratory volume in a second (FEV1) of 29% of normal values.
The blood samples were collected for whole-exome sequencing (WES) to detect mutations potentially involved in the phenotype of neuromuscular disorders observed for this patient. The genomic DNA was extracted from whole blood and subsequently subjected to whole-exome DNA library construction using the Ion AmpliSeqTM Exome RDY panel (Thermo Fisher Scientific) essentially as described in the manufacturer’s protocol, with barcode incorporation. For the sequencing, samples were loaded on an Ion HI-Q PI Chip v3 and placed onto the Ion Proton instrument (Thermo Fisher Scientific) together with an Ion PI HI-Q sequencing 200 Kit (Thermo Fisher Scientific) and sequenced for 520 cycles according to the manual (See Additional file : Table S1 for parameters). All candidate mutations found by WES were validated by direct Sanger sequencing (See Additional file : Figure S1 for the filtering process). DNA sequences were obtained from the University of California Santa Cruz (UCSC) Genome Browser. Predesigned primers were directly purchased from Thermo Fisher Scientific (See Additional file : Tables S2 for details). Amplicons were sent to Genewiz () for Sanger sequencing.
Whole exome sequencing showed that a novel variant NM_000257.3: c.1370 T > G (p.Ile457Arg) in the MYH7 gene is a missense single nucleotide variant possibly linked to the clinical findings, found in the DNA of the patient as heterozygous (Fig. ). The novel variant has been submitted to ClinVar database; with the assigned accession number SCV000804311. Two other candidate mutations were identified in the DNA of this patient, namely NM_003085.4:c.368C > A (p.Pro123His) in the SNCB gene and NM_001001557.3:c.746C > A (p.Ala249Glu) in the GDF6 gene (Additional file : Table S3). However, both mutations were discarded after filtering only genes involved in neuromuscular functions that potentially cause clinical features of muscle myopathy observed in this patient (Additional file : Figure S1). Regarding the novel variant NM_000257.3: c.1370 T > G (p.Ile457Arg), bioinformatics analyses showed that nucleotide T coding at the position 1370 of the MYH7 gene is highly conserved across 44 vertebrate species (PhyloP at 1.76). Amino acid substitution from Isoleucine (I) to Arginine (R) at the position 457 of MyHCI suggested a high impact on protein structure (Grantham at 97). Results of analyses obtained from VarSome () suggested a classification of Likely pathogenic for this variant, with evidence of Pathogenic computational results coming from 8 various prediction software including DANN, GERP, dbNSFP.FATHMM, MetaLR, MetaSVM, MutationAssessor, MutationTaster and PROVEAN (vs no benign predictions). Also, the results of analyses using the recommendation of the ACMG and the AMP suggested the same classification of Likely pathogenic for this variant, with combined criteria of 2 moderate (PM1 and PM2) and 2 supporting (PP2 and PP3) []. |
Subsets and Splits
Exclude ER emergencies
Retrieves 100 descriptions that do not contain the terms 'ER' or 'emergency', providing a basic filter of the dataset.